1. Ancestral diversity improves discovery and fine-mapping of genetic loci for anthropometric traits - the Hispanic/Latino Anthropometry Consortium
- Author
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Heather M. Highland, Francisco Rothhammer, Kristin L. Young, Andres Ruiz-Linares, Yujie Wang, Roberta McKean-Cowdin, Fernando Pires Hartwig, Noël P. Burtt, Ye Feng, Mark O. Goodarzi, Adrienne M. Stilp, Andrea R. V. R. Horimoto, Charleston W. K. Chiang, Michael Preuss, Adam G. Lilly, Gabriela Torres-Mejía, V. Saroja Voruganti, Donna E. Lehman, LáShauntá M. Glover, Roelof A.J. Smit, Yii-Der Ida Chen, Carl Langfeld, Xiuqing Guo, Rebecca Rohde, Estela Blanco, Samuel Canizales-Quinteros, Ravindranath Duggirala, Tamar Sofer, Sheila Gahagan, Anny H. Xiang, Ruth J. F. Loos, Hung-Hsin Chen, Sobha Puppala, Giovanni Poletti, Yang Hai, Claudia Schumann, Victor Acuña-Alonzo, Sharon G. Adler, Kari E. North, José Eduardo Krieger, Xinruo Zhang, Christopher A. Haiman, Alexandre C. Pereira, Thomas A. Buchanan, Xiaoyi Raymond Gao, Matthew A. Allison, Zorayr Arzumanyan, Jennifer A. Smith, Jie Yao, Marta Guindo-Martínez, Carmen R. Isasi, Clicerio González-Villalpando, Anthony G. Commuzzie, Nancy J. Cox, Kent D. Taylor, Victoria L. Buchanan, Carla Gallo, Esther M. John, Humberto García-Ortiz, David V. Conti, Lynne E. Wagenknecht, Carlos A. Aguilar-Salinas, Jose C. Florez, Willa A. Hsueh, Craig L. Hanis, Susanne B. Nicholas, Struan F.A. Grant, José de Jesús Peralta Romero, Lindsay Fernández-Rhodes, Alvin G. Thomas, Jerome I. Rotter, Maria Cátira Bortolini, Anne E. Justice, Hakon Hakonarson, Darryl Nousome, Nicholette Allred, Leslie J. Raffel, Nancy F. Butte, Wanying Zhu, Joanne E. Curran, Miguel Cruz, Xiaohui Li, Kevin Sandow, Minhui Chen, Poojan Shrestha, Eli Ipp, Teresa Tusie, Minjung Kho, Bernando Horta, Kelvin Lam, Stephanie M. Gogarten, Pauline Genter, John Blangero, Robert P. Igo, Mariaelisa Graff, Rolando González-José, Kaye Roll, Shelley A. Cole, Josep M. Mercader, Jingyi Tan, Esteban J. Parra, Jennifer E. Below, Sudha K. Iyengar, Qibin Qi, Elad Ziv, Gabriel Bedoya, Sara Pulit, Lorena Orozco, Fouad Kandeel, Astride Audirac-Chalifour, Laura Fejerman, Jerry L. Nadler, Daeeun Kim, Kaustubh Adhikari, George Papnicolaou, and Jonathan P. Bradfield
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Linkage disequilibrium ,medicine ,Locus (genetics) ,Genome-wide association study ,Anthropometry ,Overweight ,medicine.symptom ,Biology ,Population stratification ,Body mass index ,Demography ,Genetic association - Abstract
Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite notable anthropometric variability with ancestry proportions, and a high burden of growth stunting and overweight/obesity in Hispanic/Latino populations. This address this knowledge gap, we analyzed densely-imputed genetic data in a sample of Hispanic/Latino adults, to identify and fine-map common 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=59,769) and validated our findings in 9 additional studies (HISLA Stage 2, n=9,336). We conducted a trans-ethnic 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 novel BMI locus, as well two novel BMI signals and another novel height signal, each within established anthropometric loci. In our trans-ethnic meta- analysis, we identified three additional novel BMI loci, one novel height locus, and one novel WHRadjBMI locus. We also identified three secondary signals for BMI, 28 for height, and two for WHRadjBMI. We replicated >60 established anthropometric loci in Hispanic/Latino populations at genome-wide significance—representing up to 30% of previously-reported index SNP anthropometric associations. Trans-ethnic meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our novel findings demonstrate that future studies may also benefit from leveraging differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.
- Published
- 2021
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