Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

• Published in: Nature genetics Vol. 40; no. 2; pp. 189 - 197
• Main Authors: Kathiresan, Sekar, Melander, Olle, Guiducci, Candace, Surti, Aarti, Burtt, Noël P, Rieder, Mark J, Cooper, Gregory M, Roos, Charlotta, Voight, Benjamin F, Havulinna, Aki S, Wahlstrand, Björn, Hedner, Thomas, Corella, Dolores, Tai, E Shyong, Ordovas, Jose M, Berglund, Göran, Vartiainen, Erkki, Jousilahti, Pekka, Hedblad, Bo, Taskinen, Marja-Riitta, Newton-Cheh, Christopher, Salomaa, Veikko, Peltonen, Leena, Groop, Leif, Altshuler, David M, Orho-Melander, Marju
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.02.2008; Nature Publishing Group
• Subjects: Aged; Aging; Agriculture; Alleles; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood; Blood lipoproteins; Cancer Research; Cardiac and Cardiovascular Systems; Cardiology and Cardiovascular Disease; Cardiovascular diseases; Case-Control Studies; Cholesterol; Cholesterol, HDL - blood; Cholesterol, HDL - genetics; Cholesterol, LDL - blood; Cholesterol, LDL - genetics; Chromosomes; Chromosomes, Human, Pair 1; Chromosomes, Human, Pair 19; Chromosomes, Human, Pair 7; Chromosomes, Human, Pair 8; Clinical Medicine; Cohort Studies; Diagnosis; DNA; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Gene Function; Gene loci; Genetic aspects; Genetic Markers; Genetic Variation; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome; Genome, Human; HDL; Health aspects; Human; Human Genetics; Humans; Kardiologi; Kardiologi och kardiovaskulära sjukdomar; Klinisk medicin; LDL; letter; Linkage Disequilibrium; Lipids; Lipoproteins; Liver; Liver - metabolism; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Messenger; metabolism; Middle Aged; Pair 1; Pair 19; Pair 7; Pair 8; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Probability; Prospective Studies; Proteolipids; Randomized Controlled Trials as Topic; Risk factors; RNA; RNA, Messenger - metabolism; Sequence Analysis; Sequence Analysis, DNA; Single Nucleotide; Single nucleotide polymorphisms; Triglycerides; Triglycerides - blood; Triglycerides - genetics; Type 2 diabetes; Variation (Genetics); United States; Human; Lipoprotein LDL; Lipids; Lipoprotein HDL; Locus; Triglyceride; Cholesterol; Blood
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.75

Blood concentrations of lipoproteins and lipids are heritable 1 risk factors for cardiovascular disease 2 , 3 . Using genome-wide association data from three studies ( n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue 4 ) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new ( P < 5 × 10 −8 for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2 , PSRC1 and SORT1 and 19p13 near CILP2 and PBX4 ), one with HDL cholesterol (1q42 in GALNT2 ) and five with triglycerides (7q11 near TBL2 and MLXIPL , 8q24 near TRIB1 , 1q42 in GALNT2 , 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3 ). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2 , PSRC1 , and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease 5 . Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.