Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL

Anne E Justice; Kristin Young; Stephanie M Gogarten; Tamar Sofer; Misa Graff; Shelly Ann M Love; Yujie Wang; Yann C Klimentidis; Miguel Cruz; Xiuqing Guo; Fernando Hartwig; Lauren Petty; Jie Yao; Matthew A Allison; Jennifer E Below; Thomas A Buchanan; Yii-Der Ida Chen; Mark O Goodarzi; Craig Hanis; Heather M Highland; Willa A Hsueh; Eli Ipp; Esteban Parra; Walter Palmas; Leslie J Raffel; Jerome I Rotter; Jingyi Tan; Kent D Taylor; Adan Valladares; Anny H Xiang; Lisa Sánchez-Johnsen; Carmen R Isasi; Kari E North

doi:10.1093/hmg/ddab166

Genome-wide association study of body fat distribution traits in Hispanics/Latinos from the HCHS/SOL

Hum Mol Genet. 2021 Nov 1;30(22):2190-2204. doi: 10.1093/hmg/ddab166.

Authors

Anne E Justice^{1

2}, Kristin Young², Stephanie M Gogarten³, Tamar Sofer³, Misa Graff², Shelly Ann M Love², Yujie Wang², Yann C Klimentidis⁴, Miguel Cruz⁵, Xiuqing Guo⁶, Fernando Hartwig⁷, Lauren Petty⁸, Jie Yao⁶, Matthew A Allison⁹, Jennifer E Below⁸, Thomas A Buchanan¹⁰, Yii-Der Ida Chen⁶, Mark O Goodarzi¹¹, Craig Hanis¹², Heather M Highland², Willa A Hsueh¹³, Eli Ipp¹⁴, Esteban Parra¹⁵, Walter Palmas¹⁶, Leslie J Raffel¹⁷, Jerome I Rotter⁶, Jingyi Tan⁶, Kent D Taylor⁶, Adan Valladares⁵, Anny H Xiang¹⁸, Lisa Sánchez-Johnsen¹⁹, Carmen R Isasi^{20

21}, Kari E North²

Affiliations

¹ Department of Population Health Sciences, Geisinger Health System, Danville, PA 17822, USA.
² Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
³ Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
⁴ Department of Epidemiology and Biostatistics, University of Arizona, Tucson, AZ 85724, USA.
⁵ Unidad de Investigacion Medica en Bioquimica, Hospital de Especialidades, Centro Medico Nacional Siglo XXI (CMNSXX1)-IMSS, Mexico City 06720, Mexico.
⁶ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
⁷ Center for Epidemiological Research, Universidade Federal de Pelotas, Pelotas 96020, Brazil.
⁸ Division of Genetic Medicine, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
⁹ Division of Preventive Medicine, Department of Family Medicine, University of California San Diego, La Jolla, CA 92093, USA.
¹⁰ Department of Medicine, Keck School of Medicine and Diabetes and Obesity Research Institute, University of Southern California, Los Angeles, CA 90033, USA.
¹¹ Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
¹² Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
¹³ Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH 43210, USA.
¹⁴ Department of Medicine, Endocrinology, Diabetes & Metabolism, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA 90502, USA.
¹⁵ Department of Anthropology, University of Toronto at Mississauga, Mississauga, ON L5L 1C6, Canada.
¹⁶ Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
¹⁷ Department of PediatrIcs, Division of Genetic and Genomic Medicine, University of California, Irvine, CA 92868, USA.
¹⁸ Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA 91101, USA.
¹⁹ Department of Family Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
²⁰ Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10467, USA.
²¹ Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10467, USA.

Abstract

Central obesity is a leading health concern with a great burden carried by ethnic minority populations, especially Hispanics/Latinos. Genetic factors contribute to the obesity burden overall and to inter-population differences. We aimed to identify the loci associated with central adiposity measured as waist-to-hip ratio (WHR), waist circumference (WC) and hip circumference (HIP) adjusted for body mass index (adjBMI) by using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL); determine if differences in associations differ by background group within HCHS/SOL and determine whether previously reported associations generalize to HCHS/SOL. Our analyses included 7472 women and 5200 men of mainland (Mexican, Central and South American) and Caribbean (Puerto Rican, Cuban and Dominican) background residing in the USA. We performed genome-wide association analyses stratified and combined across sexes using linear mixed-model regression. We identified 16 variants for waist-to-hip ratio adjusted for body mass index (WHRadjBMI), 22 for waist circumference adjusted for body mass index (WCadjBMI) and 28 for hip circumference adjusted for body mass index (HIPadjBMI), which reached suggestive significance (P < 1 × 10-6). Many loci exhibited differences in strength of associations by ethnic background and sex. We brought a total of 66 variants forward for validation in cohorts (N = 34 161) with participants of Hispanic/Latino, African and European descent. We confirmed four novel loci (P < 0.05 and consistent direction of effect, and P < 5 × 10-8 after meta-analysis), including two for WHRadjBMI (rs13301996, rs79478137); one for WCadjBMI (rs3168072) and one for HIPadjBMI (rs28692724). Also, we generalized previously reported associations to HCHS/SOL, (8 for WHRadjBMI, 10 for WCadjBMI and 12 for HIPadjBMI). Our study highlights the importance of large-scale genomic studies in ancestrally diverse Hispanic/Latino populations for identifying and characterizing central obesity susceptibility that may be ancestry-specific.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adiposity / genetics*
Alleles
Body Fat Distribution*
Genome-Wide Association Study*
Hispanic or Latino / genetics*
Humans
Polymorphism, Single Nucleotide
Quantitative Trait, Heritable*

Abstract

Publication types

MeSH terms

Grants and funding