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Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.

TitleAncestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits-The Hispanic/Latino Anthropometry Consortium.
Publication TypePublication
Year2022
AuthorsFernández-Rhodes L, Graff M, Buchanan VL, Justice AE, Highland HM, Guo X, Zhu W, Chen H-H, Young KL, Adhikari K et al.
JournalHGG Adv
Volume3
Issue2
Pagination100099
Date Published2022 Apr 14
ISSN2666-2477
Abstract

Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

DOI10.1016/j.xhgg.2022.100099
Alternate JournalHGG Adv
PubMed ID35399580
PubMed Central IDPMC8990175
Grant ListK99 HL130580 / HL / NHLBI NIH HHS / United States
R01 HL143885 / HL / NHLBI NIH HHS / United States
P30 AG066615 / AG / NIA NIH HHS / United States
R01 HG009974 / HG / NHGRI NIH HHS / United States
R01 DK119268 / DK / NIDDK NIH HHS / United States
R00 HL130580 / HL / NHLBI NIH HHS / United States
R01 HL142302 / HL / NHLBI NIH HHS / United States
R01 HL088457 / HL / NHLBI NIH HHS / United States
U01 CA261339 / CA / NCI NIH HHS / United States
T32 HL129982 / HL / NHLBI NIH HHS / United States
R01 CA063446 / CA / NCI NIH HHS / United States
R01 CA204797 / CA / NCI NIH HHS / United States
R01 HL060712 / HL / NHLBI NIH HHS / United States
R01 HL149683 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
R01 EY022651 / EY / NEI NIH HHS / United States
F99 AG073565 / AG / NIA NIH HHS / United States
P30 ES030285 / ES / NIEHS NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
R01 HD056465 / HD / NICHD NIH HHS / United States
R01 EY014684 / EY / NEI NIH HHS / United States
U01 HG011723 / HG / NHGRI NIH HHS / United States
R01 HL140976 / HL / NHLBI NIH HHS / United States
R01 DK089256 / DK / NIDDK NIH HHS / United States
R01 DK118062 / DK / NIDDK NIH HHS / United States
UL1 TR001855 / TR / NCATS NIH HHS / United States
T32 HD091058 / HD / NICHD NIH HHS / United States
R01 HD057194 / HD / NICHD NIH HHS / United States
UL1 TR001881 / TR / NCATS NIH HHS / United States
P2C HD050924 / HD / NICHD NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
R01 DK079888 / DK / NIDDK NIH HHS / United States
R01 HG010297 / HG / NHGRI NIH HHS / United States
U10 EY011753 / EY / NEI NIH HHS / United States
R35 GM142783 / GM / NIGMS NIH HHS / United States
R01 DK122503 / DK / NIDDK NIH HHS / United States
MS#: 
0312
Manuscript Lead/Corresponding Author Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
ECI: 
Yes
Manuscript Status: 
Published