A genome-wide admixture scan identifies MYH9 as a candidate locus associated with non-diabetic end stage renal disease in African Americans

By W. Linda Kao, M. Klag, L. Meoni, David Reich, Y. Berthier-Schaad, Man Li, Josef Coresh, Nick Patterson, Arti Tandon, N. Powe and 21 more. Nature Genetics, 2008

600 citations recorded by the source corpus.

As end-stage renal disease (ESRD) has a four times higher incidence in African Americans compared to European Americans, we hypothesized that susceptibility alleles for ESRD have a higher frequency in the West African than the European gene pool. We carried out a genome-wide admixture scan in 1,372 ESRD cases and 806 controls and found a highly significant association between excess African ancestry and nondiabetic ESRD (lod score = 5.70) but not diabetic ESRD (lod = 0.47) on chromosome 22q12. Each copy of the European ancestral allele conferred a relative risk of 0.50 (95% CI = 0.39–0.63) compared to African ancestry. Multiple common SNPs (allele frequencies ranging from 0.2 to 0.6) in the gene encoding nonmuscle myosin heavy chain type II isoform A (MYH9) were associated with two to four times greater risk of nondiabetic ESRD and accounted for a large proportion of the excess risk of ESRD observed in African compared to European Americans.

Subfields: Epidemiology, Genetics

View Paper: https://www.semanticscholar.org/paper/72d279dc005f190f207ff65bc1b9c61ca2184fc5

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Citations in the corpus

• Consistent Association of Type 2 Diabetes Risk Variants Found in Europeans in Diverse Racial and Ethnic Groups (2010, background): “Individuals in the top quartile of the risk allele distribution were at 1.6 (African Americans, P = 5.361024) to 3.1-fold (Japanese Americans, P = 7.9610226) greater risk of diabetes compared to those in the lowest quartile (Table 3).”
• Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene (2010, background): “Analysis of deviance of the combined logistic regression indicates that LD with APOL1 SNP rs73885319 accounted for most of the statistical association previously attributed to the leading MYH9 variants with ESKD (supplementary material).”
• Rare Variants Create Synthetic Genome-Wide Associations (2010, unknown): “In fact, a number of recent studies have confirmed differences in effect between populations [24–35].”