Genome-wide Characterization of Shared and Distinct Genetic Components that Influence Blood Lipid Levels in Ethnically Diverse Human Populations Marc A.

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Genome-wide Characterization of Shared and Distinct Genetic Components that Influence Blood Lipid Levels in Ethnically Diverse Human Populations Marc A. Coram, Qing Duan, Thomas J. Hoffmann, Timothy Thornton, Joshua W. Knowles, Nicholas A. Johnson, Heather M. Ochs- Balcom, Timothy A. Donlon, Lisa W. Martin, Charles B. Eaton, Jennifer G. Robinson, Neil J. Risch, Xiaofeng Zhu, Charles Kooperberg, Yun Li, Alex P. Reiner, Hua Tang The American Journal of Human Genetics Volume 92, Issue 6, Pages 904-916 (June 2013) DOI: 10.1016/j.ajhg.2013.04.025 Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 1 Enrichment for Small p Values among SNPs that Are Significantly or Suggestively Associated in European GWASs (A and B) High-density lipoprotein (HDL) cholesterol in African Americans (AAs) (A) and in Hispanic Americans (HAs) (B). (C and D) Low-density lipoprotein (LDL) cholesterol in AAs (C) and in HAs (D). (E and F) Triglycerides (TG) in AAs (E) and in HAs (F). The American Journal of Human Genetics 2013 92, 904-916DOI: (10.1016/j.ajhg.2013.04.025) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 2 Genetic Effects of Candidate Lipid Variants Are Correlated between African Americans and Hispanic Americans (A–C) SNPs are those with p < 10−5 in a European GWAS. The x axis represents the estimated allelic effects in African Americans (AAs) and the y axis represents the estimated allelic effects of the corresponding SNPs in Hispanic Americans (HAs). (A) High-density lipoprotein (HDL) cholesterol. (B) Low-density lipoprotein (LDL) cholesterol. (C) Triglycerides (TG). (D) Genetic effects of 92 SNPs representing independent loci; SNPs are the best surrogate index SNPs on Affy 6.0 arrays defined by Telosvich et al.11 The estimated allelic effects in (D) are in the unit of standard deviation of the phenotype. The American Journal of Human Genetics 2013 92, 904-916DOI: (10.1016/j.ajhg.2013.04.025) Copyright © 2013 The American Society of Human Genetics Terms and Conditions

Figure 3 Overlap in Genetic Architecture in AAs Genomic regions are ranked by the SNP with the strongest association evidence in a European GWAS. Proportions of the phenotypic variance explained in AAs (y axis) by the top x% of the genome (x axis) are estimated with a mixed effect model. Red points indicates the 95% confidence interval excludes the expected value (magenta line) under the null model that x% randomly selected genome explains h2x% of phenotypic variance, where h2 is the variance explained by the entire genome. When the null cannot be excluded, the point estimates are drawn with gray points. (A) High-density lipoprotein (HDL) cholesterol. (B) Low-density lipoprotein (LDL) cholesterol. (C) Triglycerides (TG). The American Journal of Human Genetics 2013 92, 904-916DOI: (10.1016/j.ajhg.2013.04.025) Copyright © 2013 The American Society of Human Genetics Terms and Conditions