UBD modifies APOL1-induced kidney disease risk

People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1 gene APOL1 termed G1 and G2 are the causal drivers of much of this difference in risk, following a recessive pattern of inheritance. However, mo...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 115; no. 13; pp. 3446 - 3451
Main Authors Zhang, Jia-Yue, Wang, Minxian, Tian, Lei, Genovese, Giulio, Yan, Paul, Wilson, James G., Thadhani, Ravi, Mottl, Amy K., Appel, Gerald B., Bick, Alexander G., Sampson, Matthew G., Alper, Seth L., Friedman, David J., Pollak, Martin R.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 27.03.2018
Subjects
Admixtures
Alleles
Apolipoproteins
Apoptosis
Biological Sciences
Gene expression
Gene mapping
Genes
Genetic code
Genotype & phenotype
Genotypes
Health risks
Heredity
Inflammation
Kidney diseases
Kidneys
L1 gene
Loci
Phenotypes
Proteasomes
Proteins
Risk
Toxicity
Ubiquitin
FSGS
FAT10
kidney
APOL1
UBD
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Abstract People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1 gene APOL1 termed G1 and G2 are the causal drivers of much of this difference in risk, following a recessive pattern of inheritance. However, most individuals with a high-risk APOL1 genotype do not develop overt kidney disease, prompting interest in identifying those factors that interact with APOL1. We performed an admixture mapping study to identify genetic modifiers of APOL1-associated kidney disease. Individuals with two APOL1 risk alleles and focal segmental glomerulosclerosis (FSGS) have significantly increased African ancestry at the UBD (also known as FAT10) locus. UBD is a ubiquitin-like protein modifier that targets proteins for proteasomal degradation. African ancestry at the UBD locus correlates with lower levels of UBD expression. In cell-based experiments, the disease-associated APOL1 alleles (known as G1 and G2) lead to increased abundance of UBD mRNA but to decreased levels of UBD protein. UBD gene expression inversely correlates with G1 and G2 APOL1-mediated cell toxicity, as well as with levels of G1 and G2 APOL1 protein in cells. These studies support a model whereby inflammatory stimuli up-regulate both UBD and APOL1, which interact in a functionally important manner. UBD appears to mitigate APOL1-mediated toxicity by targeting it for destruction. Thus, genetically encoded differences in UBD and UBD expression appear to modify the APOL1-associated kidney phenotype.
AbstractList Two common variants in the APOL1 gene explain most of the high rate of kidney disease in people of recent African ancestry. However, not all APOL1 high-risk individuals develop kidney disease. Here we identified the UBD locus as a genetic modifier of APOL1 kidney disease using admixture mapping. Focal segmental glomerulosclerosis patients have significantly increased African ancestry at the UBD locus, which associates with lower UBD gene expression. Using a cell-based system, we show that UBD and APOL1 interact functionally and that higher levels of UBD expression mitigate APOL1 -mediated cell death. These findings are important for understanding the genetic and functional modifiers of the human APOL1 -associated phenotype and the biological pathways relevant to APOL1 -associated cell damage. People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1 gene APOL1 termed G1 and G2 are the causal drivers of much of this difference in risk, following a recessive pattern of inheritance. However, most individuals with a high-risk APOL1 genotype do not develop overt kidney disease, prompting interest in identifying those factors that interact with APOL1 . We performed an admixture mapping study to identify genetic modifiers of APOL1 -associated kidney disease. Individuals with two APOL1 risk alleles and focal segmental glomerulosclerosis (FSGS) have significantly increased African ancestry at the UBD (also known as FAT10) locus. UBD is a ubiquitin-like protein modifier that targets proteins for proteasomal degradation. African ancestry at the UBD locus correlates with lower levels of UBD expression. In cell-based experiments, the disease-associated APOL1 alleles (known as G1 and G2) lead to increased abundance of UBD mRNA but to decreased levels of UBD protein. UBD gene expression inversely correlates with G1 and G2 APOL1 -mediated cell toxicity, as well as with levels of G1 and G2 APOL1 protein in cells. These studies support a model whereby inflammatory stimuli up-regulate both UBD and APOL1 , which interact in a functionally important manner. UBD appears to mitigate APOL1 -mediated toxicity by targeting it for destruction. Thus, genetically encoded differences in UBD and UBD expression appear to modify the APOL1 -associated kidney phenotype.
Significance Two common variants in the APOL1 gene explain most of the high rate of kidney disease in people of recent African ancestry. However, not all APOL1 high-risk individuals develop kidney disease. Here we identified the UBD locus as a genetic modifier of APOL1 kidney disease using admixture mapping. Focal segmental glomerulosclerosis patients have significantly increased African ancestry at the UBD locus, which associates with lower UBD gene expression. Using a cell-based system, we show that UBD and APOL1 interact functionally and that higher levels of UBD expression mitigate APOL1 -mediated cell death. These findings are important for understanding the genetic and functional modifiers of the human APOL1 -associated phenotype and the biological pathways relevant to APOL1 -associated cell damage. People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1 gene APOL1 termed G1 and G2 are the causal drivers of much of this difference in risk, following a recessive pattern of inheritance. However, most individuals with a high-risk APOL1 genotype do not develop overt kidney disease, prompting interest in identifying those factors that interact with APOL1 . We performed an admixture mapping study to identify genetic modifiers of APOL1 -associated kidney disease. Individuals with two APOL1 risk alleles and focal segmental glomerulosclerosis (FSGS) have significantly increased African ancestry at the UBD (also known as FAT10) locus. UBD is a ubiquitin-like protein modifier that targets proteins for proteasomal degradation. African ancestry at the UBD locus correlates with lower levels of UBD expression. In cell-based experiments, the disease-associated APOL1 alleles (known as G1 and G2) lead to increased abundance of UBD mRNA but to decreased levels of UBD protein. UBD gene expression inversely correlates with G1 and G2 APOL1 -mediated cell toxicity, as well as with levels of G1 and G2 APOL1 protein in cells. These studies support a model whereby inflammatory stimuli up-regulate both UBD and APOL1 , which interact in a functionally important manner. UBD appears to mitigate APOL1 -mediated toxicity by targeting it for destruction. Thus, genetically encoded differences in UBD and UBD expression appear to modify the APOL1 -associated kidney phenotype.
People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1 gene APOL1 termed G1 and G2 are the causal drivers of much of this difference in risk, following a recessive pattern of inheritance. However, most individuals with a high-risk APOL1 genotype do not develop overt kidney disease, prompting interest in identifying those factors that interact with APOL1. We performed an admixture mapping study to identify genetic modifiers of APOL1-associated kidney disease. Individuals with two APOL1 risk alleles and focal segmental glomerulosclerosis (FSGS) have significantly increased African ancestry at the UBD (also known as FAT10) locus. UBD is a ubiquitin-like protein modifier that targets proteins for proteasomal degradation. African ancestry at the UBD locus correlates with lower levels of UBD expression. In cell-based experiments, the disease-associated APOL1 alleles (known as G1 and G2) lead to increased abundance of UBD mRNA but to decreased levels of UBD protein. UBD gene expression inversely correlates with G1 and G2 APOL1-mediated cell toxicity, as well as with levels of G1 and G2 APOL1 protein in cells. These studies support a model whereby inflammatory stimuli up-regulate both UBD and APOL1, which interact in a functionally important manner. UBD appears to mitigate APOL1-mediated toxicity by targeting it for destruction. Thus, genetically encoded differences in UBD and UBD expression appear to modify the APOL1-associated kidney phenotype.
People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1 gene termed G1 and G2 are the causal drivers of much of this difference in risk, following a recessive pattern of inheritance. However, most individuals with a high-risk genotype do not develop overt kidney disease, prompting interest in identifying those factors that interact with We performed an admixture mapping study to identify genetic modifiers of -associated kidney disease. Individuals with two risk alleles and focal segmental glomerulosclerosis (FSGS) have significantly increased African ancestry at the (also known as FAT10) locus. UBD is a ubiquitin-like protein modifier that targets proteins for proteasomal degradation. African ancestry at the locus correlates with lower levels of expression. In cell-based experiments, the disease-associated alleles (known as G1 and G2) lead to increased abundance of mRNA but to decreased levels of protein. gene expression inversely correlates with G1 and G2 -mediated cell toxicity, as well as with levels of G1 and G2 APOL1 protein in cells. These studies support a model whereby inflammatory stimuli up-regulate both and , which interact in a functionally important manner. UBD appears to mitigate -mediated toxicity by targeting it for destruction. Thus, genetically encoded differences in and expression appear to modify the -associated kidney phenotype.
Author Mottl, Amy K.
Wilson, James G.
Alper, Seth L.
Appel, Gerald B.
Tian, Lei
Yan, Paul
Genovese, Giulio
Bick, Alexander G.
Pollak, Martin R.
Thadhani, Ravi
Wang, Minxian
Sampson, Matthew G.
Friedman, David J.
Zhang, Jia-Yue
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  organization: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215
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  givenname: Minxian
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  organization: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305
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  organization: Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142
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  organization: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215
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  organization: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216
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  organization: Department of Medicine, Massachusetts General Hospital, Boston, MA 02114
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  surname: Mottl
  fullname: Mottl, Amy K.
  organization: University of North Carolina Kidney Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599
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  surname: Appel
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  organization: Center for Glomerular Diseases, Columbia University Medical Center, New York, NY 10032
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  surname: Bick
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  organization: Department of Medicine, Massachusetts General Hospital, Boston, MA 02114
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  organization: Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, MI 48109
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  organization: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215
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  organization: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215
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  givenname: Martin R.
  surname: Pollak
  fullname: Pollak, Martin R.
  organization: Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215
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Cites_doi 10.1371/journal.pgen.0020190
10.1128/MCB.25.9.3483-3491.2005
10.1681/ASN.2014111131
10.1038/nature04226
10.1371/journal.pgen.1000519
10.1681/ASN.2014050469
10.1073/pnas.0605832103
10.1016/j.molimm.2015.04.012
10.1016/j.cell.2013.02.007
10.1128/MCB.00966-05
10.1681/ASN.2016111262
10.1681/ASN.2005070692
10.1038/nm.4287
10.1371/journal.pgen.1001371
10.1371/journal.pone.0093019
10.1086/420871
10.1038/nrneph.2013.34
10.1681/ASN.2015101121
10.1242/jcs.035006
10.1007/s00439-010-0861-0
10.1126/science.1193032
10.1098/rstb.2000.0716
10.1038/ki.2014.270
10.1128/JVI.00034-09
10.1681/ASN.2011040388
10.1016/j.ajhg.2013.06.020
10.1016/j.ajhg.2017.06.005
10.1038/nature15393
10.1681/ASN.2009050479
10.1371/journal.pcbi.1000770
10.1016/j.ajhg.2013.10.012
10.1038/nature12531
10.1016/j.bbamcr.2013.01.009
10.1073/pnas.1522913113
10.1074/jbc.M105139200
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Keywords FSGS
FAT10
kidney
APOL1
UBD
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4Present address: Department of Biomedical Sciences, Cedars Sinai Medical Center, Los Angeles, CA 90048.
1J.-Y.Z. and M.W. contributed equally to this work.
3Present address: Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02142.
Author contributions: J.-Y.Z., M.W., M.G.S., S.L.A., D.J.F., and M.R.P. designed research; J.-Y.Z., M.W., P.Y., and J.G.W. performed research; J.G.W., R.T., A.K.M., and G.B.A. contributed new reagents/analytic tools; J.-Y.Z., M.W., L.T., G.G., A.G.B., S.L.A., D.J.F., and M.R.P. analyzed data; and J.-Y.Z., M.W., D.J.F., and M.R.P. wrote the paper.
Contributed by Martin R. Pollak, January 28, 2018 (sent for review September 22, 2017; reviewed by Ali Gharavi and Susan E. Quaggin)
Reviewers: A.G., Columbia University; and S.E.Q., Feinberg School of Medicine, Northwestern University.
ORCID 0000-0001-5824-9595
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References 26432245 - Nature. 2015 Oct 1;526(7571):68-74
17194218 - PLoS Genet. 2006 Dec;2(12):e190
11127900 - Philos Trans R Soc Lond B Biol Sci. 2000 Nov 29;355(1403):1553-62
28196842 - J Am Soc Nephrol. 2017 Apr;28(4):1008-1011
23910464 - Am J Hum Genet. 2013 Aug 8;93(2):278-88
24667548 - PLoS One. 2014 Mar 25;9(3):e93019
20463871 - PLoS Comput Biol. 2010 May 06;6(5):e1000770
15088269 - Am J Hum Genet. 2004 May;74(5):979-1000
19033385 - J Cell Sci. 2008 Dec 15;121(Pt 24):4079-88
19543370 - PLoS Genet. 2009 Jun;5(6):e1000519
27005919 - J Am Soc Nephrol. 2016 Oct;27(10 ):3204-3219
19959714 - J Am Soc Nephrol. 2010 Feb;21(2):316-26
21541012 - PLoS Genet. 2011 Apr;7(4):e1001371
28218918 - Nat Med. 2017 Apr;23 (4):429-438
28686856 - Am J Hum Genet. 2017 Jul 6;101(1):5-22
20647424 - Science. 2010 Aug 13;329(5993):841-5
24210251 - Am J Hum Genet. 2013 Nov 7;93(5):779-97
20635188 - Hum Genet. 2010 Sep;128(3):345-50
25983082 - Mol Immunol. 2015 Dec;68(2 Pt A):129-32
16945910 - Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14068-73
26150607 - J Am Soc Nephrol. 2016 Mar;27(3):814-23
16495380 - J Am Soc Nephrol. 2006 Apr;17(4):996-1004
19726511 - J Virol. 2009 Nov;83(22):11983-8
11445583 - J Biol Chem. 2001 Sep 21;276(38):35334-43
23452859 - Cell. 2013 Feb 28;152(5):1160-72
23438974 - Nat Rev Nephrol. 2013 Apr;9(4):240-4
21997394 - J Am Soc Nephrol. 2011 Nov;22(11):2129-37
25100047 - Kidney Int. 2015 Feb;87(2):332-42
25788523 - J Am Soc Nephrol. 2015 Nov;26(11):2882-90
16782901 - Mol Cell Biol. 2006 Jul;26(13):5180-9
26699492 - Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):830-7
16255080 - Nature. 2005 Oct 27;437(7063):1299-320
24037378 - Nature. 2013 Sep 26;501(7468):506-11
23333871 - Biochim Biophys Acta. 2014 Jan;1843(1):97-102
15831455 - Mol Cell Biol. 2005 May;25(9):3483-91
Freedman ML (e_1_3_4_17_2) 2006; 103
Sampson MG (e_1_3_4_10_2) 2016; 27
Patterson N (e_1_3_4_16_2) 2004; 74
Pasaniuc B (e_1_3_4_11_2) 2011; 7
Olabisi OA (e_1_3_4_26_2) 2016; 113
Fan Y (e_1_3_4_9_2) 2014; 9
Patterson N (e_1_3_4_22_2) 2006; 2
Nichols B (e_1_3_4_24_2) 2015; 87
Hipp MS (e_1_3_4_8_2) 2005; 25
Snyder A (e_1_3_4_29_2) 2009; 83
Kopp JB (e_1_3_4_3_2) 2011; 22
Visscher PM (e_1_3_4_19_2) 2017; 101
Maples BK (e_1_3_4_12_2) 2013; 93
Canaan A (e_1_3_4_27_2) 2006; 26
Schmidtke G (e_1_3_4_6_2) 2014; 1843
International HapMap Consortium (e_1_3_4_15_2) 2005; 437
Genovese G (e_1_3_4_1_2) 2010; 329
Raasi S (e_1_3_4_28_2) 2001; 276
Tzur S (e_1_3_4_2_2) 2010; 128
Basler M (e_1_3_4_7_2) 2015; 68
Bruggeman LA (e_1_3_4_5_2) 2017; 28
Genovese G (e_1_3_4_18_2) 2013; 9
Price AL (e_1_3_4_13_2) 2009; 5
Lappalainen T (e_1_3_4_21_2) 2013; 501
Kalveram B (e_1_3_4_35_2) 2008; 121
Stegle O (e_1_3_4_23_2) 2010; 6
Gong P (e_1_3_4_25_2) 2010; 21
Kasembeli AN (e_1_3_4_4_2) 2015; 26
Kozlitina J (e_1_3_4_33_2) 2016; 27
Barton NH (e_1_3_4_31_2) 2000; 355
Beckerman P (e_1_3_4_32_2) 2017; 23
Ross MJ (e_1_3_4_34_2) 2006; 17
Merbl Y (e_1_3_4_30_2) 2013; 152
Auton A (e_1_3_4_14_2) 2015; 526
Edwards SL (e_1_3_4_20_2) 2013; 93
References_xml – volume: 2
  start-page: e190
  year: 2006
  ident: e_1_3_4_22_2
  article-title: Population structure and eigenanalysis
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.0020190
  contributor:
    fullname: Patterson N
– volume: 25
  start-page: 3483
  year: 2005
  ident: e_1_3_4_8_2
  article-title: FAT10, a ubiquitin-independent signal for proteasomal degradation
  publication-title: Mol Cell Biol
  doi: 10.1128/MCB.25.9.3483-3491.2005
  contributor:
    fullname: Hipp MS
– volume: 27
  start-page: 814
  year: 2016
  ident: e_1_3_4_10_2
  article-title: Integrative genomics identifies novel associations with APOL1 risk genotypes in black NEPTUNE subjects
  publication-title: J Am Soc Nephrol
  doi: 10.1681/ASN.2014111131
  contributor:
    fullname: Sampson MG
– volume: 437
  start-page: 1299
  year: 2005
  ident: e_1_3_4_15_2
  article-title: A haplotype map of the human genome
  publication-title: Nature
  doi: 10.1038/nature04226
  contributor:
    fullname: International HapMap Consortium
– volume: 5
  start-page: e1000519
  year: 2009
  ident: e_1_3_4_13_2
  article-title: Sensitive detection of chromosomal segments of distinct ancestry in admixed populations
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1000519
  contributor:
    fullname: Price AL
– volume: 26
  start-page: 2882
  year: 2015
  ident: e_1_3_4_4_2
  article-title: APOL1 risk variants are strongly associated with HIV-associated nephropathy in black South Africans
  publication-title: J Am Soc Nephrol
  doi: 10.1681/ASN.2014050469
  contributor:
    fullname: Kasembeli AN
– volume: 103
  start-page: 14068
  year: 2006
  ident: e_1_3_4_17_2
  article-title: Admixture mapping identifies 8q24 as a prostate cancer risk locus in African-American men
  publication-title: Proc Natl Acad Sci USA
  doi: 10.1073/pnas.0605832103
  contributor:
    fullname: Freedman ML
– volume: 68
  start-page: 129
  year: 2015
  ident: e_1_3_4_7_2
  article-title: The ubiquitin-like modifier FAT10 in antigen processing and antimicrobial defense
  publication-title: Mol Immunol
  doi: 10.1016/j.molimm.2015.04.012
  contributor:
    fullname: Basler M
– volume: 152
  start-page: 1160
  year: 2013
  ident: e_1_3_4_30_2
  article-title: Profiling of ubiquitin-like modifications reveals features of mitotic control
  publication-title: Cell
  doi: 10.1016/j.cell.2013.02.007
  contributor:
    fullname: Merbl Y
– volume: 26
  start-page: 5180
  year: 2006
  ident: e_1_3_4_27_2
  article-title: FAT10/diubiquitin-like protein-deficient mice exhibit minimal phenotypic differences
  publication-title: Mol Cell Biol
  doi: 10.1128/MCB.00966-05
  contributor:
    fullname: Canaan A
– volume: 28
  start-page: 1008
  year: 2017
  ident: e_1_3_4_5_2
  article-title: Identifying the intracellular function of APOL1
  publication-title: J Am Soc Nephrol
  doi: 10.1681/ASN.2016111262
  contributor:
    fullname: Bruggeman LA
– volume: 17
  start-page: 996
  year: 2006
  ident: e_1_3_4_34_2
  article-title: Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal disease
  publication-title: J Am Soc Nephrol
  doi: 10.1681/ASN.2005070692
  contributor:
    fullname: Ross MJ
– volume: 23
  start-page: 429
  year: 2017
  ident: e_1_3_4_32_2
  article-title: Transgenic expression of human APOL1 risk variants in podocytes induces kidney disease in mice
  publication-title: Nat Med
  doi: 10.1038/nm.4287
  contributor:
    fullname: Beckerman P
– volume: 7
  start-page: e1001371
  year: 2011
  ident: e_1_3_4_11_2
  article-title: Enhanced statistical tests for GWAS in admixed populations: Assessment using African Americans from CARe and a breast cancer consortium
  publication-title: PLoS Genet
  doi: 10.1371/journal.pgen.1001371
  contributor:
    fullname: Pasaniuc B
– volume: 9
  start-page: e93019
  year: 2014
  ident: e_1_3_4_9_2
  article-title: Temporal profile of the renal transcriptome of HIV-1 transgenic mice during disease progression
  publication-title: PLoS One
  doi: 10.1371/journal.pone.0093019
  contributor:
    fullname: Fan Y
– volume: 74
  start-page: 979
  year: 2004
  ident: e_1_3_4_16_2
  article-title: Methods for high-density admixture mapping of disease genes
  publication-title: Am J Hum Genet
  doi: 10.1086/420871
  contributor:
    fullname: Patterson N
– volume: 9
  start-page: 240
  year: 2013
  ident: e_1_3_4_18_2
  article-title: APOL1 variants and kidney disease in people of recent African ancestry
  publication-title: Nat Rev Nephrol
  doi: 10.1038/nrneph.2013.34
  contributor:
    fullname: Genovese G
– volume: 27
  start-page: 3204
  year: 2016
  ident: e_1_3_4_33_2
  article-title: Plasma levels of risk-variant APOL1 do not associate with renal disease in a population-based cohort
  publication-title: J Am Soc Nephrol
  doi: 10.1681/ASN.2015101121
  contributor:
    fullname: Kozlitina J
– volume: 121
  start-page: 4079
  year: 2008
  ident: e_1_3_4_35_2
  article-title: The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition
  publication-title: J Cell Sci
  doi: 10.1242/jcs.035006
  contributor:
    fullname: Kalveram B
– volume: 128
  start-page: 345
  year: 2010
  ident: e_1_3_4_2_2
  article-title: Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene
  publication-title: Hum Genet
  doi: 10.1007/s00439-010-0861-0
  contributor:
    fullname: Tzur S
– volume: 329
  start-page: 841
  year: 2010
  ident: e_1_3_4_1_2
  article-title: Association of trypanolytic ApoL1 variants with kidney disease in African Americans
  publication-title: Science
  doi: 10.1126/science.1193032
  contributor:
    fullname: Genovese G
– volume: 355
  start-page: 1553
  year: 2000
  ident: e_1_3_4_31_2
  article-title: Genetic hitchhiking
  publication-title: Philos Trans R Soc Lond B Biol Sci
  doi: 10.1098/rstb.2000.0716
  contributor:
    fullname: Barton NH
– volume: 87
  start-page: 332
  year: 2015
  ident: e_1_3_4_24_2
  article-title: Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1
  publication-title: Kidney Int
  doi: 10.1038/ki.2014.270
  contributor:
    fullname: Nichols B
– volume: 83
  start-page: 11983
  year: 2009
  ident: e_1_3_4_29_2
  article-title: FAT10: A novel mediator of Vpr-induced apoptosis in human immunodeficiency virus-associated nephropathy
  publication-title: J Virol
  doi: 10.1128/JVI.00034-09
  contributor:
    fullname: Snyder A
– volume: 22
  start-page: 2129
  year: 2011
  ident: e_1_3_4_3_2
  article-title: APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy
  publication-title: J Am Soc Nephrol
  doi: 10.1681/ASN.2011040388
  contributor:
    fullname: Kopp JB
– volume: 93
  start-page: 278
  year: 2013
  ident: e_1_3_4_12_2
  article-title: RFMix: A discriminative modeling approach for rapid and robust local-ancestry inference
  publication-title: Am J Hum Genet
  doi: 10.1016/j.ajhg.2013.06.020
  contributor:
    fullname: Maples BK
– volume: 101
  start-page: 5
  year: 2017
  ident: e_1_3_4_19_2
  article-title: 10 years of GWAS discovery: Biology, function, and translation
  publication-title: Am J Hum Genet
  doi: 10.1016/j.ajhg.2017.06.005
  contributor:
    fullname: Visscher PM
– volume: 526
  start-page: 68
  year: 2015
  ident: e_1_3_4_14_2
  article-title: A global reference for human genetic variation
  publication-title: Nature
  doi: 10.1038/nature15393
  contributor:
    fullname: Auton A
– volume: 21
  start-page: 316
  year: 2010
  ident: e_1_3_4_25_2
  article-title: The ubiquitin-like protein FAT10 mediates NF-kappaB activation
  publication-title: J Am Soc Nephrol
  doi: 10.1681/ASN.2009050479
  contributor:
    fullname: Gong P
– volume: 6
  start-page: e1000770
  year: 2010
  ident: e_1_3_4_23_2
  article-title: A Bayesian framework to account for complex non-genetic factors in gene expression levels greatly increases power in eQTL studies
  publication-title: PLOS Comput Biol
  doi: 10.1371/journal.pcbi.1000770
  contributor:
    fullname: Stegle O
– volume: 93
  start-page: 779
  year: 2013
  ident: e_1_3_4_20_2
  article-title: Beyond GWASs: Illuminating the dark road from association to function
  publication-title: Am J Hum Genet
  doi: 10.1016/j.ajhg.2013.10.012
  contributor:
    fullname: Edwards SL
– volume: 501
  start-page: 506
  year: 2013
  ident: e_1_3_4_21_2
  article-title: Transcriptome and genome sequencing uncovers functional variation in humans
  publication-title: Nature
  doi: 10.1038/nature12531
  contributor:
    fullname: Lappalainen T
– volume: 1843
  start-page: 97
  year: 2014
  ident: e_1_3_4_6_2
  article-title: FAT10ylation as a signal for proteasomal degradation
  publication-title: Biochim Biophys Acta
  doi: 10.1016/j.bbamcr.2013.01.009
  contributor:
    fullname: Schmidtke G
– volume: 113
  start-page: 830
  year: 2016
  ident: e_1_3_4_26_2
  article-title: APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases
  publication-title: Proc Natl Acad Sci USA
  doi: 10.1073/pnas.1522913113
  contributor:
    fullname: Olabisi OA
– volume: 276
  start-page: 35334
  year: 2001
  ident: e_1_3_4_28_2
  article-title: The ubiquitin-like protein FAT10 forms covalent conjugates and induces apoptosis
  publication-title: J Biol Chem
  doi: 10.1074/jbc.M105139200
  contributor:
    fullname: Raasi S
SSID ssj0009580
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Snippet People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1...
Significance Two common variants in the APOL1 gene explain most of the high rate of kidney disease in people of recent African ancestry. However, not all APOL1...
Two common variants in the APOL1 gene explain most of the high rate of kidney disease in people of recent African ancestry. However, not all APOL1 high-risk...
SourceID pubmedcentral
proquest
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pubmed
jstor
SourceType Open Access Repository
Aggregation Database
Index Database
Publisher
StartPage 3446
SubjectTerms Admixtures
Alleles
Apolipoproteins
Apoptosis
Biological Sciences
Gene expression
Gene mapping
Genes
Genetic code
Genotype & phenotype
Genotypes
Health risks
Heredity
Inflammation
Kidney diseases
Kidneys
L1 gene
Loci
Phenotypes
Proteasomes
Proteins
Risk
Toxicity
Ubiquitin
Title UBD modifies APOL1-induced kidney disease risk
URI https://www.jstor.org/stable/26508246
https://www.ncbi.nlm.nih.gov/pubmed/29531077
https://www.proquest.com/docview/2101331209
https://search.proquest.com/docview/2013519146
https://pubmed.ncbi.nlm.nih.gov/PMC5879665
Volume 115
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