Dataset Information

Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

ABSTRACT: Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ?2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ?50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p?=?8.8×10(-7) and p?=?1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p?=?13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.

SUBMITTER: Elbers CC

PROVIDER: S-EPMC3517599 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

Elbers Clara C CC Guo Yiran Y Tragante Vinicius V van Iperen Erik P A EP Lanktree Matthew B MB Castillo Berta Almoguera BA Chen Fang F Yanek Lisa R LR Wojczynski Mary K MK Li Yun R YR Ferwerda Bart B Ballantyne Christie M CM Buxbaum Sarah G SG Chen Yii-Der Ida YD Chen Wei-Min WM Cupples L Adrienne LA Cushman Mary M Duan Yanan Y Duggan David D Evans Michele K MK Fernandes Jyotika K JK Fornage Myriam M Garcia Melissa M Garvey W Timothy WT Glazer Nicole N Gomez Felicia F Harris Tamara B TB Halder Indrani I Howard Virginia J VJ Keller Margaux F MF Kamboh M Ilyas MI Kooperberg Charles C Kritchevsky Stephen B SB LaCroix Andrea A Liu Kiang K Liu Yongmei Y Musunuru Kiran K Newman Anne B AB Onland-Moret N Charlotte NC Ordovas Jose J Peter Inga I Post Wendy W Redline Susan S Reis Steven E SE Saxena Richa R Schreiner Pamela J PJ Volcik Kelly A KA Wang Xingbin X Yusuf Salim S Zonderland Alan B AB Anand Sonia S SS Becker Diane M DM Psaty Bruce B Rader Daniel J DJ Reiner Alex P AP Rich Stephen S SS Rotter Jerome I JI Sale Michèle M MM Tsai Michael Y MY Borecki Ingrid B IB Hegele Robert A RA Kathiresan Sekar S Nalls Michael A MA Taylor Herman A HA Hakonarson Hakon H Sivapalaratnam Suthesh S Asselbergs Folkert W FW Drenos Fotios F Wilson James G JG Keating Brendan J BJ

PloS one 20121207 12

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance lev ...[more]

PMID: 23236364

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Project description:To investigate the polygenicity of complex traits in populations of East Asian (EAS) and European (EUR) descents, we leveraged genome-wide data from Biobank Japan, UK Biobank, and FinnGen cohorts. Specifically, we analyzed up to 215 outcomes related to 18 health domains, assessing their polygenic architecture via descriptive statistics, such as the proportion of susceptibility SNPs per trait (πc). While we did not observe EAS-EUR differences in the overall distribution of polygenicity parameters across the phenotypes investigated, there were ancestry-specific patterns in the polygenicity differences between health domains. In EAS, pairwise comparisons across health domains showed enrichment for πc differences related to hematological and metabolic traits (hematological fold-enrichment = 4.45, p = 2.15 × 10-7; metabolic fold-enrichment = 4.05, p = 4.01 × 10-6). For both categories, the proportion of susceptibility SNPs was lower than that observed for several other health domains (EAS-hematological median πc = 0.15%, EAS-metabolic median πc = 0.18%) with the strongest πc difference with respect to respiratory traits (EAS-respiratory median πc = 0.50%; hematological-p = 2.26 × 10-3; metabolic-p = 3.48 × 10-3). In EUR, pairwise comparisons showed multiple πc differences related to the endocrine category (fold-enrichment = 5.83, p = 4.76 × 10-6), where these traits showed a low proportion of susceptibility SNPs (EUR-endocrine median πc = 0.01%) with the strongest difference with respect to psychiatric phenotypes (EUR-psychiatric median πc = 0.50%; p = 1.19 × 10-4). Simulating sample sizes of 1,000,000 and 5,000,000 individuals, we also showed that ancestry-specific polygenicity patterns translate into differences across health domains in the genetic variance explained by susceptibility SNPs projected to be genome-wide significant (e.g., EAS hematological-neoplasm p = 2.18 × 10-4; EUR endocrine-gastrointestinal p = 6.80 × 10-4). These findings highlight that traits related to the same health domains may present ancestry-specific variability in their polygenicity.

Dataset Information

Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

Publications

Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

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