Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population
Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin conc...
Saved in:
| Published in | Nutrients Vol. 11; no. 1; p. 90 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
MDPI AG
04.01.2019
MDPI |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2072-6643 2072-6643 |
| DOI | 10.3390/nu11010090 |
Cover
Loading…
| Abstract | Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55–75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10−8 (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 × 10−24), rs4148324 (p = 9.48 × 10−24), rs6742078 (p = 1.29 × 10−23), rs887829 (p = 1.39 × 10−23), and the rs4148324 (p = 9.48 × 10−24)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 × 10−11) and women (p = 2.15 × 10−14), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 × 10−5). We did not detect any gene-MedDiet interaction at p < 1 × 10−5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10−5, and even at the GWAS level for the IL17B gene (p = 3.14 × 10−8). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet. |
|---|---|
| AbstractList | Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55–75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10−8 (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 × 10−24), rs4148324 (p = 9.48 × 10−24), rs6742078 (p = 1.29 × 10−23), rs887829 (p = 1.39 × 10−23), and the rs4148324 (p = 9.48 × 10−24)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 × 10−11) and women (p = 2.15 × 10−14), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 × 10−5). We did not detect any gene-MedDiet interaction at p < 1 × 10−5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10−5, and even at the GWAS level for the IL17B gene (p = 3.14 × 10−8). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet. Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55–75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10 −8 (GWAS level). The top-ranked were four SNPs (rs4148325 ( p = 9.25 × 10 −24 ), rs4148324 ( p = 9.48 × 10 −24 ), rs6742078 ( p = 1.29 × 10 −23 ), rs887829 ( p = 1.39 × 10 −23 ), and the rs4148324 ( p = 9.48 × 10 −24 )) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men ( p = 4.77 × 10 −11 ) and women ( p = 2.15 × 10 −14 ), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance ( p < 1 × 10 −5 ). We did not detect any gene-MedDiet interaction at p < 1 × 10 −5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10 −5 , and even at the GWAS level for the IL17B gene ( p = 3.14 × 10 −8 ). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet. Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55⁻75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at < 5 × 10 (GWAS level). The top-ranked were four SNPs (rs4148325 ( = 9.25 × 10 ), rs4148324 ( = 9.48 × 10 ), rs6742078 ( = 1.29 × 10 ), rs887829 ( = 1.39 × 10 ), and the rs4148324 ( = 9.48 × 10 )) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men ( = 4.77 × 10 ) and women ( = 2.15 × 10 ), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance ( < 1 × 10 ). We did not detect any gene-MedDiet interaction at < 1 × 10 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at < 1 × 10 , and even at the GWAS level for the IL17B gene ( = 3.14 × 10 ). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet. Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55⁻75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10-8 (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 × 10-24), rs4148324 (p = 9.48 × 10-24), rs6742078 (p = 1.29 × 10-23), rs887829 (p = 1.39 × 10-23), and the rs4148324 (p = 9.48 × 10-24)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 × 10-11) and women (p = 2.15 × 10-14), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 × 10-5). We did not detect any gene-MedDiet interaction at p < 1 × 10-5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10-5, and even at the GWAS level for the IL17B gene (p = 3.14 × 10-8). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet.Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55⁻75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10-8 (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 × 10-24), rs4148324 (p = 9.48 × 10-24), rs6742078 (p = 1.29 × 10-23), rs887829 (p = 1.39 × 10-23), and the rs4148324 (p = 9.48 × 10-24)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 × 10-11) and women (p = 2.15 × 10-14), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 × 10-5). We did not detect any gene-MedDiet interaction at p < 1 × 10-5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10-5, and even at the GWAS level for the IL17B gene (p = 3.14 × 10-8). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet. |
| Author | Martínez-LaCruz, Raul Ortega-Azorín, Carolina Coltell, Oscar Asensio, Eva M. Barragán, Rocio Ordovas, Jose M. González, José I. Gimenez-Alba, Ignacio Fitó, Montserrat Sorlí, José V. Ros, Emilio Fernández-Carrión, Rebeca Zanón-Moreno, Vicente Corella, Dolores Portolés, Olga |
| AuthorAffiliation | 10 Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain 1 Department of Computer Languages and Systems, Universitat Jaume I, 12071 Castellón, Spain; oscar.coltell@uji.es 11 IMDEA Alimentación, 28049 Madrid, Spain 4 Area of Health Sciences, Valencian International University, 46002 Valencia, Spain; vczanon@universidadviu.com 6 Ophthalmology Research Unit “Santiago Grisolia”, Dr. Peset University Hospital, 46017 Valencia, Spain 5 Red Temática de Investigación Cooperativa OftaRed, Instituto de Salud Carlos III, 28029 Madrid, Spain 3 Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain; nachoga16@gmail.com 7 Instituto Hospital del Mar de Investigaciones Médicas, 08003 Barcelona, Spain 2 CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain; eva.m.asensio@uv.es (E.M.A.); jose.sorli@uv.es (J.V.S.) |
| AuthorAffiliation_xml | – name: 10 Department of Cardiovascular Epidemiology and Population Genetics, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain – name: 1 Department of Computer Languages and Systems, Universitat Jaume I, 12071 Castellón, Spain; oscar.coltell@uji.es – name: 2 CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain; eva.m.asensio@uv.es (E.M.A.); jose.sorli@uv.es (J.V.S.); rocio.barragan@uv.es (R.B.); Rebeca.Fernandez@uv.es (R.F.-C.); Olga.Portoles@uv.es (O.P.); carolina.ortega@uv.es (C.O.-A.); raulmartinezlacruz@gmail.com (R.M.-L.); Ignacio.Glez-Arraez@uv.es (J.I.G.); Mfito@imim.es (M.F.); EROS@clinic.cat (E.R.) – name: 9 Nutrition and Genomics Laboratory, JM-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA; jose.ordovas@tufts.edu – name: 11 IMDEA Alimentación, 28049 Madrid, Spain – name: 6 Ophthalmology Research Unit “Santiago Grisolia”, Dr. Peset University Hospital, 46017 Valencia, Spain – name: 8 Lipid Clinic, Endocrinology and Nutrition Service, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, University of Barcelona, 08036 Barcelona, Spain – name: 4 Area of Health Sciences, Valencian International University, 46002 Valencia, Spain; vczanon@universidadviu.com – name: 3 Department of Preventive Medicine and Public Health, School of Medicine, University of Valencia, 46010 Valencia, Spain; nachoga16@gmail.com – name: 5 Red Temática de Investigación Cooperativa OftaRed, Instituto de Salud Carlos III, 28029 Madrid, Spain – name: 7 Instituto Hospital del Mar de Investigaciones Médicas, 08003 Barcelona, Spain |
| Author_xml | – sequence: 1 givenname: Oscar orcidid: 0000-0002-4518-8495 surname: Coltell fullname: Coltell, Oscar – sequence: 2 givenname: Eva M. surname: Asensio fullname: Asensio, Eva M. – sequence: 3 givenname: José V. orcidid: 0000-0002-0130-2006 surname: Sorlí fullname: Sorlí, José V. – sequence: 4 givenname: Rocio orcidid: 0000-0001-8072-3791 surname: Barragán fullname: Barragán, Rocio – sequence: 5 givenname: Rebeca surname: Fernández-Carrión fullname: Fernández-Carrión, Rebeca – sequence: 6 givenname: Olga surname: Portolés fullname: Portolés, Olga – sequence: 7 givenname: Carolina surname: Ortega-Azorín fullname: Ortega-Azorín, Carolina – sequence: 8 givenname: Raul surname: Martínez-LaCruz fullname: Martínez-LaCruz, Raul – sequence: 9 givenname: José I. surname: González fullname: González, José I. – sequence: 10 givenname: Vicente orcidid: 0000-0003-1179-1592 surname: Zanón-Moreno fullname: Zanón-Moreno, Vicente – sequence: 11 givenname: Ignacio surname: Gimenez-Alba fullname: Gimenez-Alba, Ignacio – sequence: 12 givenname: Montserrat surname: Fitó fullname: Fitó, Montserrat – sequence: 13 givenname: Emilio orcidid: 0000-0002-2573-1294 surname: Ros fullname: Ros, Emilio – sequence: 14 givenname: Jose M. surname: Ordovas fullname: Ordovas, Jose M. – sequence: 15 givenname: Dolores orcidid: 0000-0002-2366-4104 surname: Corella fullname: Corella, Dolores |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/30621171$$D View this record in MEDLINE/PubMed |
| BookMark | eNqFkt1qFDEUgAep2B974wNIwJsqjOZvkp1eCOuqa6GiMEovQyZzxmaZTdYkU91H8-3M7ra1FsHcJDn58uWccA6LPecdFMUTgl8yVuNXbiQEE4xr_KA4oFjSUgjO9u6s94vjGBd4MySWgj0q9hkWlBBJDopfc3B-CeWF7QBNY_TG6mS9Q00auzU6mV9Mm-co79_YwYaxtQ7NvDPgUthyEeVIM7YLMCmiHzZdoo-QdOsHa1Czdl3I9lPUwM-yWYGxfQ5vnGjq9LCONiLtOpSTgPKthYTOXIKgza1aZ11ncyxoB9qhz341DtuXHxcPez1EOL6ej4qv7999mX0ozz_Nz2bT89JwVqdSUOgmhPa8MoxPZF91vaQSAxGY9S2tDZaspsAnjFUaJl3Ha457KaSBWgA37Kh4vfOuxnYJ3a70Qa2CXeqwVl5b9feJs5fqm79SglVC1CILTq4FwX8fISa1tNHAMOSK_BgVpRNR04ow-X-UiOzkuK4y-uweuvBjyJ-aKYYpFbxiNFNP7yZ_m_VNA2QA7wATfIwBemVs2v5vrsUOimC1aTP1p83ylRf3rtxY_wH_BgWC0zk |
| CitedBy_id | crossref_primary_10_1038_s41598_024_71217_5 crossref_primary_10_1007_s00228_023_03549_6 crossref_primary_10_3389_fnut_2023_1119768 crossref_primary_10_3390_ijtm4040052 crossref_primary_10_3390_ijerph20043635 crossref_primary_10_1002_alz_13507 crossref_primary_10_1016_j_seizure_2023_10_004 crossref_primary_10_1111_bcp_16009 crossref_primary_10_3390_nu13020541 crossref_primary_10_3390_genes12070991 crossref_primary_10_3390_nu12113323 crossref_primary_10_1371_journal_pgen_1009464 crossref_primary_10_3390_ijms26072980 crossref_primary_10_1371_journal_pone_0280344 crossref_primary_10_2147_DMSO_S464671 crossref_primary_10_3390_nu12020310 crossref_primary_10_1136_gutjnl_2021_326314 crossref_primary_10_1371_journal_pone_0229374 crossref_primary_10_3390_biomedicines10010079 crossref_primary_10_1016_j_jhep_2023_06_004 crossref_primary_10_21518_ms2024_212 crossref_primary_10_3390_antiox12112004 crossref_primary_10_2217_pgs_2020_0049 crossref_primary_10_3390_genes13030420 |
| Cites_doi | 10.1016/j.jacc.2015.11.029 10.1002/gepi.21748 10.1371/journal.pgen.1004228 10.1038/srep29240 10.1016/S0021-9150(00)00420-2 10.1186/s12966-018-0741-x 10.1002/mnfr.201700347 10.1371/journal.pone.0138677 10.1161/HYPERTENSIONAHA.118.11130 10.1002/hep.1840400412 10.1371/journal.pone.0172253 10.1093/hmg/ddq281 10.1186/s13742-015-0047-8 10.1186/s12863-015-0291-z 10.1161/ATVBAHA.117.310071 10.1053/j.gastro.2017.01.041 10.1016/j.cca.2018.10.028 10.1016/j.clinre.2012.03.028 10.1016/j.trre.2018.06.003 10.1007/978-3-319-77932-4_38 10.1371/journal.pone.0168148 10.1111/cts.12590 10.1038/ncomms10558 10.1371/journal.pone.0153427 10.1093/hmg/ddp203 10.1080/07853890.2017.1377846 10.1093/hmg/ddp202 10.1186/s12944-018-0857-7 10.1161/JAHA.117.007792 10.1016/j.immuni.2015.03.008 10.1016/j.gde.2018.02.009 10.1086/519795 10.1016/j.tig.2018.07.004 10.1016/j.jdiacomp.2018.08.006 10.1136/bmj.k2173 10.1161/CIRCULATIONAHA.106.633206 10.1093/clinchem/47.1.81 10.1007/s11255-018-1923-9 10.1124/mol.116.107524 10.1016/j.molmed.2016.07.004 10.1096/fj.15-279554 10.1101/005165 10.1016/j.tem.2015.10.004 10.1093/bioinformatics/bth457 10.1186/s12929-018-0475-8 10.1016/S0002-9149(01)01494-1 10.1371/journal.pone.0198974 10.1002/hep.29599 10.1111/acer.12786 10.1152/ajpheart.00417.2017 10.1002/gepi.21711 10.1016/j.bbadis.2014.05.002 10.1038/ejhg.2011.206 10.1152/physiolgenomics.00004.2015 10.1038/ng.2581 10.1038/505612a 10.1016/S2352-4642(18)30139-1 10.1016/j.jpeds.2014.01.060 10.1016/j.ejmg.2018.04.012 10.1002/oby.22074 10.1096/fj.10-166454 10.1152/ajprenal.00039.2014 10.1038/s41598-017-02514-5 10.3851/IMP2747 10.1001/jamanetworkopen.2018.1670 10.1373/clinchem.2010.151043 10.1155/2018/6905720 10.1002/gepi.21977 10.1371/journal.pone.0033988 10.1016/j.molmet.2018.04.007 10.1101/gr.137323.112 10.4065/mcp.2011.0178 10.1073/pnas.1811086115 10.1016/j.mehy.2006.12.069 10.1007/s00431-011-1641-0 |
| ContentType | Journal Article |
| Copyright | 2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2019 by the authors. 2019 |
| Copyright_xml | – notice: 2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. – notice: 2019 by the authors. 2019 |
| DBID | AAYXX CITATION NPM 3V. 7TS 7X7 7XB 88E 8FI 8FJ 8FK ABUWG AFKRA AZQEC BENPR CCPQU DWQXO FYUFA GHDGH K9. M0S M1P PHGZM PHGZT PIMPY PJZUB PKEHL PPXIY PQEST PQQKQ PQUKI PRINS 7X8 7S9 L.6 5PM |
| DOI | 10.3390/nu11010090 |
| DatabaseName | CrossRef PubMed ProQuest Central (Corporate) Physical Education Index Health & Medical Collection ProQuest Central (purchase pre-March 2016) Medical Database (Alumni Edition) Hospital Premium Collection Hospital Premium Collection (Alumni Edition) ProQuest Central (Alumni) (purchase pre-March 2016) ProQuest Central (Alumni) ProQuest Central UK/Ireland ProQuest Central Essentials ProQuest Central ProQuest One ProQuest Central ProQuest Health Research Premium Collection Health Research Premium Collection (Alumni) ProQuest Health & Medical Complete (Alumni) ProQuest Health & Medical Collection Medical Database ProQuest Central Premium ProQuest One Academic (New) Publicly Available Content Database ProQuest Health & Medical Research Collection ProQuest One Academic Middle East (New) ProQuest One Health & Nursing ProQuest One Academic Eastern Edition (DO NOT USE) ProQuest One Academic ProQuest One Academic UKI Edition ProQuest Central China MEDLINE - Academic AGRICOLA AGRICOLA - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef PubMed Publicly Available Content Database ProQuest One Academic Middle East (New) ProQuest Central Essentials ProQuest Health & Medical Complete (Alumni) ProQuest Central (Alumni Edition) ProQuest One Community College ProQuest One Health & Nursing ProQuest Central China Physical Education Index ProQuest Central ProQuest Health & Medical Research Collection Health Research Premium Collection Health and Medicine Complete (Alumni Edition) ProQuest Central Korea Health & Medical Research Collection ProQuest Central (New) ProQuest Medical Library (Alumni) ProQuest One Academic Eastern Edition ProQuest Hospital Collection Health Research Premium Collection (Alumni) ProQuest Hospital Collection (Alumni) ProQuest Health & Medical Complete ProQuest Medical Library ProQuest One Academic UKI Edition ProQuest One Academic ProQuest One Academic (New) ProQuest Central (Alumni) MEDLINE - Academic AGRICOLA AGRICOLA - Academic |
| DatabaseTitleList | CrossRef AGRICOLA PubMed MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: BENPR name: ProQuest Central url: https://www.proquest.com/central sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Anatomy & Physiology |
| EISSN | 2072-6643 |
| ExternalDocumentID | PMC6356696 30621171 10_3390_nu11010090 |
| Genre | Journal Article |
| GeographicLocations | Spain |
| GeographicLocations_xml | – name: Spain |
| GrantInformation_xml | – fundername: Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) grantid: PRX17/00500 – fundername: Real Colegio Complutense at Harvard University grantid: Dolores Corella research stay – fundername: Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) grantid: PI06/1326 – fundername: University Jaume I grantid: COGRUP/2016/06 – fundername: Generalitat Valenciana grantid: AEST/2018/044 – fundername: Fundació La Marató de TV3 grantid: 538/U/2016 – fundername: Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) grantid: SAF2016-80532-R – fundername: Generalitat Valenciana grantid: PROMETEO2017/017 – fundername: Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) grantid: CIBER 06/03 – fundername: Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) grantid: PI16/00366 |
| GroupedDBID | --- 53G 5VS 7X7 88E 8FE 8FH 8FI 8FJ A8Z AADQD AAFWJ AAHBH AAWTL AAYXX ABUWG ACIWK ACPRK AENEX AFKRA AFRAH AFZYC ALIPV ALMA_UNASSIGNED_HOLDINGS APEBS BENPR BPHCQ BVXVI CCPQU CITATION DIK E3Z EBD ECGQY EIHBH ESTFP EYRJQ F5P FYUFA GX1 HMCUK HYE KQ8 LK8 M1P M48 MODMG M~E OK1 P2P P6G PGMZT PHGZM PHGZT PIMPY PQQKQ PROAC PSQYO RNS RPM TR2 UKHRP NPM 3V. 7TS 7XB 8FK AZQEC DWQXO K9. PJZUB PKEHL PPXIY PQEST PQUKI PRINS 7X8 7S9 L.6 5PM |
| ID | FETCH-LOGICAL-c439t-62ed812f45c3487f5df7270e1603fb29c07392e48335ae8dd4940f767ce96e4c3 |
| IEDL.DBID | 7X7 |
| ISSN | 2072-6643 |
| IngestDate | Thu Aug 21 14:14:37 EDT 2025 Mon Jul 21 10:16:14 EDT 2025 Mon Jul 21 10:13:49 EDT 2025 Fri Jul 25 19:54:31 EDT 2025 Thu Apr 03 06:56:51 EDT 2025 Thu Apr 24 22:57:45 EDT 2025 Tue Jul 01 02:30:28 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 1 |
| Keywords | bilirubin Mediterranean gene-diet interaction sex-specific GWAS UGT1A1 |
| Language | English |
| License | https://creativecommons.org/licenses/by/4.0 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c439t-62ed812f45c3487f5df7270e1603fb29c07392e48335ae8dd4940f767ce96e4c3 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| ORCID | 0000-0003-1179-1592 0000-0002-2366-4104 0000-0002-4518-8495 0000-0002-2573-1294 0000-0001-8072-3791 0000-0002-0130-2006 |
| OpenAccessLink | https://www.proquest.com/docview/2302264532?pq-origsite=%requestingapplication% |
| PMID | 30621171 |
| PQID | 2302264532 |
| PQPubID | 2032353 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_6356696 proquest_miscellaneous_2286925137 proquest_miscellaneous_2165664095 proquest_journals_2302264532 pubmed_primary_30621171 crossref_citationtrail_10_3390_nu11010090 crossref_primary_10_3390_nu11010090 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 20190104 |
| PublicationDateYYYYMMDD | 2019-01-04 |
| PublicationDate_xml | – month: 1 year: 2019 text: 20190104 day: 4 |
| PublicationDecade | 2010 |
| PublicationPlace | Switzerland |
| PublicationPlace_xml | – name: Switzerland – name: Basel |
| PublicationTitle | Nutrients |
| PublicationTitleAlternate | Nutrients |
| PublicationYear | 2019 |
| Publisher | MDPI AG MDPI |
| Publisher_xml | – name: MDPI AG – name: MDPI |
| References | Ding (ref_25) 2011; 25 Kang (ref_51) 2010; 19 ref_14 ref_58 Johnson (ref_50) 2009; 18 Sanna (ref_55) 2009; 18 ref_52 Dearden (ref_6) 2018; 15 Lin (ref_76) 2006; 114 Boon (ref_37) 2014; 307 Schiebinger (ref_11) 2016; 67 ref_18 ref_17 Boyle (ref_66) 2012; 22 Zuo (ref_71) 2015; 39 ref_59 Liu (ref_35) 2018; 32 Fretzayas (ref_26) 2012; 171 Germain (ref_70) 2013; 45 ref_61 ref_60 Kerkhof (ref_10) 2018; Volume 1065 Barrett (ref_65) 2005; 21 Yueh (ref_78) 2017; 91 Chen (ref_21) 2019; 488 Cheriyath (ref_38) 2010; 2 Lai (ref_36) 2018; 50 ref_68 ref_67 McKiernan (ref_80) 2012; 36 ref_20 Rinaldi (ref_27) 2015; 45 ref_64 ref_62 Gauderman (ref_15) 2013; 37 Seigneur (ref_69) 2018; 115 Munroe (ref_5) 2015; 47 ref_29 ref_28 Hofker (ref_4) 2014; 1842 Amor (ref_41) 2017; 37 Maruo (ref_79) 2014; 165 Reynolds (ref_81) 2015; 42 Fujiwara (ref_33) 2018; 67 Olusanya (ref_30) 2018; 2 ref_32 Levy (ref_23) 2001; 87 ref_75 Vazquez (ref_3) 2018; 34 Chen (ref_56) 2012; 20 ref_74 ref_73 Hunt (ref_48) 2001; 154 Bulmer (ref_22) 2018; 315 ref_39 Lin (ref_44) 2010; 56 Uludag (ref_43) 2018; 50 Matsuura (ref_72) 2017; 152 Atanasovska (ref_1) 2015; 26 Zhang (ref_16) 2016; 40 Zeng (ref_7) 2018; 1 Hinds (ref_46) 2018; 72 Clayton (ref_13) 2016; 30 McCarty (ref_77) 2007; 69 ref_47 ref_45 Dai (ref_53) 2013; 37 Purcell (ref_63) 2007; 81 Liu (ref_34) 2018; 2018 Gao (ref_8) 2018; 26 ref_40 Bathum (ref_24) 2001; 47 Smith (ref_19) 2018; 62 Sundararaghavan (ref_42) 2018; 32 Nelson (ref_57) 2014; 19 ref_9 Loos (ref_2) 2018; 50 Zucker (ref_49) 2004; 40 Bielinski (ref_54) 2011; 86 Gazzin (ref_31) 2016; 22 Collins (ref_12) 2014; 505 |
| References_xml | – volume: 67 start-page: 136 year: 2016 ident: ref_11 article-title: Gender Matters in Biological Research and Medical Practice publication-title: J. Am. Coll. Cardiol. doi: 10.1016/j.jacc.2015.11.029 – volume: 37 start-page: 603 year: 2013 ident: ref_15 article-title: Finding Novel Genes by Testing G × E Interactions in a Genome-Wide Association Study: Scanning for G × E Interaction to Find New Genes publication-title: Genet. Epidemiol. doi: 10.1002/gepi.21748 – ident: ref_17 doi: 10.1371/journal.pgen.1004228 – ident: ref_32 doi: 10.1038/srep29240 – volume: 154 start-page: 747 year: 2001 ident: ref_48 article-title: Association of plasma bilirubin with coronary heart disease and segregation of bilirubin as a major gene trait: The NHLBI family heart study publication-title: Atherosclerosis doi: 10.1016/S0021-9150(00)00420-2 – ident: ref_60 doi: 10.1186/s12966-018-0741-x – volume: 62 start-page: 1700347 year: 2018 ident: ref_19 article-title: Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent publication-title: Mol. Nutr. Food Res. doi: 10.1002/mnfr.201700347 – ident: ref_52 doi: 10.1371/journal.pone.0138677 – volume: 72 start-page: 788 year: 2018 ident: ref_46 article-title: Bilirubin, a Cardiometabolic Signaling Molecule publication-title: Hypertension doi: 10.1161/HYPERTENSIONAHA.118.11130 – volume: 40 start-page: 827 year: 2004 ident: ref_49 article-title: Serum bilirubin levels in the U.S. population: Gender effect and inverse correlation with colorectal cancer publication-title: Hepatology doi: 10.1002/hep.1840400412 – ident: ref_59 doi: 10.1371/journal.pone.0172253 – volume: 19 start-page: 3672 year: 2010 ident: ref_51 article-title: Genome-wide association of serum bilirubin levels in Korean population publication-title: Hum. Mol. Genet. doi: 10.1093/hmg/ddq281 – ident: ref_64 doi: 10.1186/s13742-015-0047-8 – ident: ref_39 doi: 10.1186/s12863-015-0291-z – volume: 37 start-page: 2356 year: 2017 ident: ref_41 article-title: Relationship Between Total Serum Bilirubin Levels and Carotid and Femoral Atherosclerosis in Familial DyslipidemiaHighlights publication-title: Arterioscler. Thromb. Vasc. Biol. doi: 10.1161/ATVBAHA.117.310071 – volume: 152 start-page: 1383 year: 2017 ident: ref_72 article-title: Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection publication-title: Gastroenterology doi: 10.1053/j.gastro.2017.01.041 – volume: 488 start-page: 1 year: 2019 ident: ref_21 article-title: Serum bilirubin improves the risk predictions of cardiovascular and total death in diabetic patients publication-title: Clin. Chim. Acta doi: 10.1016/j.cca.2018.10.028 – volume: 36 start-page: 287 year: 2012 ident: ref_80 article-title: Metabolic liver disease publication-title: Clin. Res. Hepatol. Gastroenterol. doi: 10.1016/j.clinre.2012.03.028 – volume: 32 start-page: 234 year: 2018 ident: ref_42 article-title: Bilirubin, a new therapeutic for kidney transplant? publication-title: Transplant. Rev. doi: 10.1016/j.trre.2018.06.003 – ident: ref_58 – volume: Volume 1065 start-page: 627 year: 2018 ident: ref_10 article-title: Genome-Wide Association Studies and Risk Scores for Coronary Artery Disease: Sex Biases publication-title: Sex-Specific Analysis of Cardiovascular Function doi: 10.1007/978-3-319-77932-4_38 – ident: ref_61 doi: 10.1371/journal.pone.0168148 – ident: ref_75 doi: 10.1111/cts.12590 – ident: ref_9 doi: 10.1038/ncomms10558 – ident: ref_45 doi: 10.1371/journal.pone.0153427 – volume: 18 start-page: 2711 year: 2009 ident: ref_55 article-title: Common variants in the SLCO1B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia publication-title: Hum. Mol. Genet. doi: 10.1093/hmg/ddp203 – volume: 50 start-page: 16 year: 2018 ident: ref_36 article-title: Direct, indirect and total bilirubin and risk of incident coronary heart disease in the Dongfeng-Tongji cohort publication-title: Ann. Med. doi: 10.1080/07853890.2017.1377846 – volume: 18 start-page: 2700 year: 2009 ident: ref_50 article-title: Genome-wide association meta-analysis for total serum bilirubin levels publication-title: Hum. Mol. Genet. doi: 10.1093/hmg/ddp202 – ident: ref_47 doi: 10.1186/s12944-018-0857-7 – ident: ref_20 doi: 10.1161/JAHA.117.007792 – volume: 42 start-page: 692 year: 2015 ident: ref_81 article-title: Interleukin-17B Antagonizes Interleukin-25-Mediated Mucosal Inflammation publication-title: Immunity doi: 10.1016/j.immuni.2015.03.008 – volume: 50 start-page: 86 year: 2018 ident: ref_2 article-title: The genetics of adiposity publication-title: Curr. Opin. Genet. Dev. doi: 10.1016/j.gde.2018.02.009 – volume: 81 start-page: 559 year: 2007 ident: ref_63 article-title: PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses publication-title: Am. J. Hum. Genet. doi: 10.1086/519795 – volume: 34 start-page: 746 year: 2018 ident: ref_3 article-title: Complex-Trait Prediction in the Era of Big Data publication-title: Trends Genet. doi: 10.1016/j.tig.2018.07.004 – volume: 32 start-page: 1012 year: 2018 ident: ref_35 article-title: Bilirubin and its changes were negatively associated with diabetic kidney disease incidence and progression: A five-year’s cohort study based on 5323 Chinese male diabetic patients publication-title: J. Diabetes Its Complicat. doi: 10.1016/j.jdiacomp.2018.08.006 – ident: ref_14 doi: 10.1136/bmj.k2173 – volume: 114 start-page: 1476 year: 2006 ident: ref_76 article-title: Association Between the UGT1A1*28 Allele, Bilirubin Levels, and Coronary Heart Disease in the Framingham Heart Study publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.106.633206 – volume: 47 start-page: 81 year: 2001 ident: ref_24 article-title: Evidence for a substantial genetic influence on biochemical liver function tests: Results from a population-based Danish twin study publication-title: Clin. Chem. doi: 10.1093/clinchem/47.1.81 – ident: ref_28 – volume: 50 start-page: 1695 year: 2018 ident: ref_43 article-title: Serum bilirubin level and its impact on the progression of chronic kidney disease publication-title: Int. Urol. Nephrol. doi: 10.1007/s11255-018-1923-9 – volume: 91 start-page: 545 year: 2017 ident: ref_78 article-title: Developmental, Genetic, Dietary, and Xenobiotic Influences on Neonatal Hyperbilirubinemia publication-title: Mol. Pharmacol. doi: 10.1124/mol.116.107524 – volume: 45 start-page: 202 year: 2015 ident: ref_27 article-title: The combination of new missense mutation with (A(TA)7TAA) dinucleotide repeat in UGT1A1 gene promoter causes Gilbert’s syndrome publication-title: Ann. Clin. Lab. Sci. – volume: 22 start-page: 758 year: 2016 ident: ref_31 article-title: A Novel Perspective on the Biology of Bilirubin in Health and Disease publication-title: Trends Mol. Med. doi: 10.1016/j.molmed.2016.07.004 – volume: 30 start-page: 519 year: 2016 ident: ref_13 article-title: Studying both sexes: A guiding principle for biomedicine publication-title: FASEB J. doi: 10.1096/fj.15-279554 – ident: ref_67 doi: 10.1101/005165 – volume: 2 start-page: 201 year: 2010 ident: ref_38 article-title: High Total Bilirubin as a Protective Factor for Diabetes Mellitus: An Analysis of NHANES Data from 1999–2006 publication-title: J. Clin. Med. Res. – volume: 26 start-page: 722 year: 2015 ident: ref_1 article-title: GWAS as a Driver of Gene Discovery in Cardiometabolic Diseases publication-title: Trends Endocrinol. Metab. doi: 10.1016/j.tem.2015.10.004 – volume: 21 start-page: 263 year: 2005 ident: ref_65 article-title: Haploview: Analysis and visualization of LD and haplotype maps publication-title: Bioinformatics doi: 10.1093/bioinformatics/bth457 – ident: ref_29 doi: 10.1186/s12929-018-0475-8 – volume: 87 start-page: 1196 year: 2001 ident: ref_23 article-title: Total serum bilirubin and risk of cardiovascular disease in the Framingham offspring study publication-title: Am. J. Cardiol. doi: 10.1016/S0002-9149(01)01494-1 – ident: ref_62 doi: 10.1371/journal.pone.0198974 – volume: 67 start-page: 1609 year: 2018 ident: ref_33 article-title: Systemic regulation of bilirubin homeostasis: Potential benefits of hyperbilirubinemia publication-title: Hepatology doi: 10.1002/hep.29599 – volume: 39 start-page: 1388 year: 2015 ident: ref_71 article-title: A New Genomewide Association Meta-Analysis of Alcohol Dependence publication-title: Alcohol. Clin. Exp. Res. doi: 10.1111/acer.12786 – ident: ref_40 – volume: 315 start-page: H429 year: 2018 ident: ref_22 article-title: Bilirubin acts as a multipotent guardian of cardiovascular integrity: More than just a radical idea publication-title: Am. J. Physiol.-Heart Circ. Physiol. doi: 10.1152/ajpheart.00417.2017 – volume: 37 start-page: 293 year: 2013 ident: ref_53 article-title: A Genome-Wide Association Study for Serum Bilirubin Levels and Gene-Environment Interaction in a Chinese Population publication-title: Genet. Epidemiol. doi: 10.1002/gepi.21711 – volume: 1842 start-page: 1889 year: 2014 ident: ref_4 article-title: The genome revolution and its role in understanding complex diseases publication-title: Biochim. Biophys. Acta doi: 10.1016/j.bbadis.2014.05.002 – volume: 20 start-page: 463 year: 2012 ident: ref_56 article-title: UGT1A1 is a major locus influencing bilirubin levels in African Americans publication-title: Eur. J. Hum. Genet. doi: 10.1038/ejhg.2011.206 – ident: ref_18 – volume: 47 start-page: 365 year: 2015 ident: ref_5 article-title: Genome-wide association studies and contribution to cardiovascular physiology publication-title: Physiol. Genom. doi: 10.1152/physiolgenomics.00004.2015 – volume: 45 start-page: 518 year: 2013 ident: ref_70 article-title: Genome-wide association analysis identifies a susceptibility locus for pulmonary arterial hypertension publication-title: Nat. Genet. doi: 10.1038/ng.2581 – volume: 505 start-page: 612 year: 2014 ident: ref_12 article-title: Policy: NIH plans to enhance reproducibility publication-title: Nature doi: 10.1038/505612a – volume: 2 start-page: 610 year: 2018 ident: ref_30 article-title: Neonatal hyperbilirubinaemia: A global perspective publication-title: Lancet Child Adolesc. Health doi: 10.1016/S2352-4642(18)30139-1 – volume: 165 start-page: 36 year: 2014 ident: ref_79 article-title: Bilirubin Uridine Diphosphate-Glucuronosyltransferase Variation Is a Genetic Basis of Breast Milk Jaundice publication-title: J. Pediatr. doi: 10.1016/j.jpeds.2014.01.060 – ident: ref_74 doi: 10.1016/j.ejmg.2018.04.012 – volume: 26 start-page: 202 year: 2018 ident: ref_8 article-title: Genome-Wide Study of Subcutaneous and Visceral Adipose Tissue Reveals Novel Sex-Specific Adiposity Loci in Mexican Americans: Genetics of Adipose Deposition publication-title: Obesity doi: 10.1002/oby.22074 – volume: 25 start-page: 301 year: 2011 ident: ref_25 article-title: The coordinated increased expression of biliverdin reductase and heme oxygenase-2 promotes cardiomyocyte survival: A reductase-based peptide counters β-adrenergic receptor ligand-mediated cardiac dysfunction publication-title: FASEB J. doi: 10.1096/fj.10-166454 – volume: 307 start-page: F123 year: 2014 ident: ref_37 article-title: Circulating bilirubin and defense against kidney disease and cardiovascular mortality: Mechanisms contributing to protection in clinical investigations publication-title: Am. J. Physiol.-Ren. Physiol. doi: 10.1152/ajprenal.00039.2014 – ident: ref_73 doi: 10.1038/s41598-017-02514-5 – volume: 19 start-page: 679 year: 2014 ident: ref_57 article-title: Genome-wide association study to characterize serum bilirubin elevations in patients with HCV treated with GS-9256, an HCV NS3 serine protease inhibitor publication-title: Antivir. Ther. doi: 10.3851/IMP2747 – volume: 1 start-page: e181670 year: 2018 ident: ref_7 article-title: Sex Differences in Genetic Associations With Longevity publication-title: JAMA Netw. Open doi: 10.1001/jamanetworkopen.2018.1670 – volume: 56 start-page: 1535 year: 2010 ident: ref_44 article-title: Serum Bilirubin and Genes Controlling Bilirubin Concentrations as Biomarkers for Cardiovascular Disease publication-title: Clin. Chem. doi: 10.1373/clinchem.2010.151043 – volume: 2018 start-page: 1 year: 2018 ident: ref_34 article-title: The U-Shaped Association between Bilirubin and Diabetic Retinopathy Risk: A Five-Year Cohort Based on 5323 Male Diabetic Patients publication-title: J. Diabetes Res. doi: 10.1155/2018/6905720 – volume: 40 start-page: 394 year: 2016 ident: ref_16 article-title: Detecting Gene-Environment Interactions for a Quantitative Trait in a Genome-Wide Association Study: Detecting Gene-Environment Interactions for a Quantitative publication-title: Genet. Epidemiol. doi: 10.1002/gepi.21977 – ident: ref_68 doi: 10.1371/journal.pone.0033988 – volume: 15 start-page: 8 year: 2018 ident: ref_6 article-title: Sex and gender differences in developmental programming of metabolism publication-title: Mol. Metab. doi: 10.1016/j.molmet.2018.04.007 – volume: 22 start-page: 1790 year: 2012 ident: ref_66 article-title: Annotation of functional variation in personal genomes using RegulomeDB publication-title: Genome Res. doi: 10.1101/gr.137323.112 – volume: 86 start-page: 606 year: 2011 ident: ref_54 article-title: Mayo Genome Consortia: A Genotype-Phenotype Resource for Genome-Wide Association Studies with an Application to the Analysis of Circulating Bilirubin Levels publication-title: Mayo Clin. Proc. doi: 10.4065/mcp.2011.0178 – volume: 115 start-page: E10235 year: 2018 ident: ref_69 article-title: Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular projections and contribute to different behavioral outputs publication-title: Proc. Natl. Acad. Sci. USA doi: 10.1073/pnas.1811086115 – volume: 69 start-page: 974 year: 2007 ident: ref_77 article-title: ‘“Iatrogenic Gilbert syndrome”’—A strategy for reducing vascular and cancer risk by increasing plasma unconjugated bilirubin publication-title: Med. Hypotheses doi: 10.1016/j.mehy.2006.12.069 – volume: 171 start-page: 11 year: 2012 ident: ref_26 article-title: Eponym: Gilbert syndrome publication-title: Eur. J. Pediatr. doi: 10.1007/s00431-011-1641-0 |
| SSID | ssj0000070763 |
| Score | 2.3273365 |
| Snippet | Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with... |
| SourceID | pubmedcentral proquest pubmed crossref |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source |
| StartPage | 90 |
| SubjectTerms | antioxidants bilirubin blood serum Cardiovascular disease cardiovascular diseases Cytokines gender genes genome-wide association study Genomes glucuronosyltransferases Haplotypes Health care Hospitals jaundice lead liver diseases loci Mediterranean diet men Metabolic syndrome Metabolism nutrigenomics Nutrition research nutrition-genotype interaction Population single nucleotide polymorphism women |
| SummonAdditionalLinks | – databaseName: Scholars Portal Journals: Open Access dbid: M48 link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3fb9MwELam8cILAsaPwECHQIg9GNrEcRokhMpgm5CKkEq1vUWJfRaROhfaVFr_NP477vKLdUx7jHOJIp-d-76z_Z0Qr3AQRUZZ4iZhjlLFxsqRiZVEZ4fWmSTCgvOQk2_6ZKa-nsVnO6Kr39l24Opaasf1pGbL-duL35uPNOE_MOMkyv7OrymGDQksEHW_RREp4RIOkxbmNzA4IboeNeqkVx7Zjkf_gcyreyUvBZ-ju-JOixph3Lj5nthBf1_sjT0x5vMNvIZ6H2edIN8Tf47RL85RnpYW4VLvA28Z3MCb49Px9ADo-lM5L5drYsZwyGcXfSuguwJqof8JJ2hWwHlamGBFY2VeGpi2AgfvYYoXsi5e76iZ3wmdvgnk3gLLWcvPJVZQ5xyb4xP1q3PgxSFqoyiJuYfvfQmxB2J29OXH4YlsCzRIQzimkjpESwDBkYsjIj4uto7g0AC5dLUrwtTwMmCIig925TiyVqVq4BKdGEw1KhM9FLt-4fGxgDC1xiqiX6ElyhlHeeEwHhUaCy7agioQB52bMtOql3MRjXlGLIZdmv1zaSBe9ra_Gs2Oa632O29n3bDLiJDxyeI4CgPxor9NM46XUahXFmuyYcEiTbw4vsEmHOmUoGOUBOJRM4D6TyGSRqw7GQYi2RpavQErfm_f8eXPWvmbxQR1qp_c_OlPxW2CdWmdKFL7YrdarvEZQaeqeF7Pi7_BIhyy priority: 102 providerName: Scholars Portal |
| Title | Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/30621171 https://www.proquest.com/docview/2302264532 https://www.proquest.com/docview/2165664095 https://www.proquest.com/docview/2286925137 https://pubmed.ncbi.nlm.nih.gov/PMC6356696 |
| Volume | 11 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwfV3fb9MwELZge-EFAeNHYEyHQIg9WGtjJ2l4Qd3YOiF1mijT-hYl9kWL1LljTSX2p_Hfceek2QpoL5Fin6LI5x_fd7a_E-ID9pQy2hI3CXOUOjJWDkykJZa2b0uTKCw4Djk-iY_P9LdpNG0Dbov2WOVqTvQTtZ0bjpHvEVTmO5-RCr9c_ZScNYp3V9sUGg_FJkuXMflKpkkXY_FaNrFqVEkVsfs9t6Tlrk-4ore-Dv0DLv8-I3ln0Tl6Ih63aBGGjXufigfonomtoSOmfHkDH8Gf3_SB8S3xe4RufonyvLIId1od-KjgDXwanQ8nu0Dv-9Wsul4SI4YDvrPoWuHcBVAJzSMcmFkAx2dhjDX1kVllYNIKG3yGCf6SPml9ScX8TVjpmkDuLLCMtfxaYQ0-1thcm_CfzoE3haiMVkfMHZx2qcOei7Ojwx8Hx7JNzCAN4ZdaxiFaAgYluVYR4SkjWxIM6iGnrC6LMDW8_Rei5gtdOQ6s1anulUmcGExj1Ea9EBtu7vCVgDC1xmqiXaElqhmpvCgxGhQxFpysBXUgdlduykyrWs7JM2YZsRd2aXbr0kC872yvGq2O_1ptr7ydteN1kd32rkC866pppPH2CbXKfEk2LFQUEx-O7rEJB3FKkFElgXjZdKDuV4icEdtO-oFI1rpWZ8BK3-s1rrrwit8sIhin8ev7f_2NeERwLvUBIr0tNurrJb4lyFQXO35c7IjN_cOT0-_0Npr26TnWgz_ARR5E |
| linkProvider | ProQuest |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9NAEF6VcoALAgrUUGAQD9GDVce7tmMkhEJLm9KmQkqr5mbs3bGwlDqhcQT5U9z5d8z41QZQbz3aHq1Wntmd-WZnvxHiFTpSamUIm7gx2srTxu5qT9mYmo5JdSAx4Tzk4Mjvn6jPI2-0In41d2G4rLLZE8uN2kw058i3KFTmO5-edD9Mv9vcNYpPV5sWGpVZHODiB0G22fv9HdLva9fd_XS83bfrrgK2Judb2L6LhrxaSvOSFK2nnknJhzvI_ZbTxA01n125qPg2UoxdY1SonDTwA42hj0pLGveGuEmO1-ESwmAUtDmdkjvHlxULqpShs5XPyb12KI5xlv3eP8Hs3zWZl5zc7l1xp45OoVeZ0z2xgvl9sdbLCZmfLeANlPWiZSJ-Tfzew3xyhvZpZhAuaRm4NHEBb_dOe8NNoOeP2Tg7nxMCh22-I5nXRL0zoDe0b3EiaAacD4YBFmST40zDsCZSeAdD_GkPp1iWDgKPCQ2PCsS5AabNtncyLKDMbVbXNMqhY-BDKHpH3hjjHL60rcoeiJNrUdlDsZpPclwX4IZGG0UwzzUEbT0ZJyl63cTHhJvDoLLEZqOmSNcs6dysYxwRWmKVRhcqtcTLVnZacYP8V2qj0XZU7w-z6MKaLfGi_Uwrm49r6K9M5iTDxEg-4W_vChm364cUosrAEo8qA2qnQmCQ0H3QsUSwZFqtADOLL3_Js28lwziTFvqh__jqqT8Xt_rHg8PocP_o4Im4TaFkWCan1IZYLc7n-JTCtSJ5Vq4REF-ve1H-AR1pVqI |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9NAEF6VIiEuCCgPQ4FBPEQPVhzv2o6REAoNaUtpVSlUzc3Yu2NhKXVC4wjy0-DXMeNXG0C99Wh7tFp5ZnYeO_ONEC_RkVIrQ7GJG6OtPG3snvaUjanpmlQHEhPOQx4c-rvH6tPYG6-J300vDJdVNmdieVCbqeYceYdcZe759KTbSeuyiKPB8P3su80TpPimtRmnUYnIPi5_UPg2f7c3IF6_ct3hxy_bu3Y9YcDWZIgL23fRkIVLaY-SPPfUMynZcwd59nKauKHmeywXFXcmxdgzRoXKSQM_0Bj6qLSkda-J64Eks0m6FIyDNr9T4uj4skJElTJ0OvmCTG2XfBpn1Qb-49j-XZ95weANb4tbtacK_Uq07og1zO-KjX5OUfrpEl5DWTtaJuU3xK8dzKenaJ9kBuECx4HLFJfwZuekP9oCev6QTbKzBUXjsM39knkN2jsHekNnGCeF5sC5YTjAguRzkmkY1aAKb2GEP-3RDMsyQuA1ocFUgTg3wBDa9iDDAso8Z9WyUS4dA19I0TuyzBjncNSOLbsnjq-EZffFej7N8aEANzTaKAr5XENhrifjJEWvl_iY8KAYVJbYatgU6RoxnQd3TCKKnJil0TlLLfGipZ1VOCH_pdpsuB3VZ8U8OpdsSzxvP5OW89UN_ZXpgmgYJMmnWNy7hMbt-SG5qzKwxINKgNqtUGBIkX7QtUSwIlotAaOMr37Js28l2jgDGPqh_-jyrT8TN0gdo897h_uPxU3yKsMyT6U2xXpxtsAn5LkVydNSRUB8vWqd_APcplrY |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Genome-Wide+Association+Study+%28GWAS%29+on+Bilirubin+Concentrations+in+Subjects+with+Metabolic+Syndrome%3A+Sex-Specific+GWAS+Analysis+and+Gene-Diet+Interactions+in+a+Mediterranean+Population&rft.jtitle=Nutrients&rft.au=Coltell%2C+Oscar&rft.au=Asensio%2C+Eva+M&rft.au=Sorl%C3%AD%2C+Jos%C3%A9+V&rft.au=Barrag%C3%A1n%2C+Rocio&rft.date=2019-01-04&rft.pub=MDPI+AG&rft.eissn=2072-6643&rft.volume=11&rft.issue=1&rft.spage=90&rft_id=info:doi/10.3390%2Fnu11010090&rft.externalDBID=HAS_PDF_LINK |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2072-6643&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2072-6643&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2072-6643&client=summon |