HGG advances · 2022

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

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Fernández-Rhodes Lindsay, Graff Mariaelisa, Buchanan Victoria L, Justice Anne E, Highland Heather M, Guo Xiuqing, Zhu Wanying, Chen Hung-Hsin, Young Kristin L, Adhikari Kaustubh, Palmer Nicholette D, Below Jennifer E, Bradfield Jonathan, Pereira Alexandre C, Glover LáShauntá, Kim Daeeun, Lilly Adam G, Shrestha Poojan, Thomas Alvin G, Zhang Xinruo, Chen Minhui, Chiang Charleston W K, Pulit Sara, Horimoto Andrea, Krieger Jose E, Guindo-Martínez Marta, Preuss Michael, Schumann Claudia, Smit Roelof A J, Torres-Mejía Gabriela, Acuña-Alonzo Victor, Bedoya Gabriel, Bortolini Maria-Cátira, Canizales-Quinteros Samuel, Gallo Carla, González-José Rolando, Poletti Giovanni, Rothhammer Francisco, Hakonarson Hakon, Igo Robert, Adler Sharon G, Iyengar Sudha K, Nicholas Susanne B, Gogarten Stephanie M, Isasi Carmen R, Papnicolaou George, Stilp Adrienne M, Qi Qibin, Kho Minjung, Smith Jennifer A, Langefeld Carl D, Wagenknecht Lynne, Mckean-Cowdin Roberta, Gao Xiaoyi Raymond, Nousome Darryl, Conti David V, Feng Ye, Allison Matthew A, Arzumanyan Zorayr, Buchanan Thomas A, Ida Chen Yii-Der, Genter Pauline M, Goodarzi Mark O, Hai Yang, Hsueh Willa, Ipp Eli, Kandeel Fouad R, Lam Kelvin, Li Xiaohui, Nadler Jerry L, Raffel Leslie J, Roll Kathryn, Sandow Kevin, Tan Jingyi, Taylor Kent D, Xiang Anny H, Yao Jie, Audirac-Chalifour Astride, de Jesus Peralta Romero Jose, Hartwig Fernando, Horta Bernando, Blangero John, Curran Joanne E, Duggirala Ravindranath, Lehman Donna E, Puppala Sobha, Fejerman Laura, John Esther M, Aguilar-Salinas Carlos, Burtt Noël P, Florez Jose C, García-Ortíz Humberto, González-Villalpando Clicerio, Mercader Josep, Orozco Lorena, Tusié-Luna Teresa, Blanco Estela, Gahagan Sheila, Cox Nancy J, Hanis Craig, Butte Nancy F, Cole Shelley A, Comuzzie Anthony G, Voruganti V Saroja, Rohde Rebecca, Wang Yujie, Sofer Tamar, Ziv Elad, Grant Struan F A, Ruiz-Linares Andres, Rotter Jerome I, Haiman Christopher A, Parra Esteban J, Cruz Miguel, Loos Ruth J F, North Kari E

Аннотация

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.

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

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