Genetic ancestry influences gene-environment interactions with sociocultural factors: Results from the Hispanic Community Health Study/Study of Latinos
Often, studies will aggregate all participants identified as Hispanic/Latino, despite genetic and environmental substructures, preventing the meaningful interrogation of the roles of genetics and environment in human health. Using the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we examined how self-identified background group and genetic ancestry influence gene-environment interactions between body mass index (BMI) and a polygenic score for BMI (PGS<sub>BMI</sub>). Participants (n = 7,075) identified with six background groups: Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American. Generalized linear models incorporating complex survey weighting were used to model BMI through joint and stratified (background group, estimated Amerindigenous [AME] ancestry) analyses including PGS<sub>BMI</sub> and other health-related variables. Interaction effects were modeled between PGS<sub>BMI</sub> and diet and age at immigration. Comparing pooled to background group-stratified analyses, we observe heterogeneous distributions of environmental and sociocultural variables, as well as differing associations with AME ancestry. Within the multivariate model, PGS<sub>BMI</sub> performance decreased with increasing AME ancestry. After stratification, PGS-age-at-immigration interactions remained statistically significant in some strata: Mexican background individuals born in the US (50 states/DC) (β = 1.33, p < 0.01), Dominican background individuals 6-12 years old (β = 4.38, p < 0.001), and Cuban background individuals 0-5 years old (β = 2.20, p = 0.015) relative to those ≥ 21 years old at migration. It is vital to understand populations of interest to model them appropriately and prevent possible confounding or misinterpretation. While this work focuses specifically on Hispanic/Latino groups, these lessons are relevant to other groups as we diversify work to better understand gene-environment interactions.
Authors
- Christina Cordero (ORCID: https://orcid.org/0000-0003-1032-5303)
- Gregory A. Talavera (ORCID: https://orcid.org/0000-0001-5360-1107)
- Krista M. Perreira (ORCID: https://orcid.org/0000-0003-2906-0261)
- Cristin E. McArdle (ORCID: https://orcid.org/0000-0003-4115-8771)
- Genevieve L. Wojcik (ORCID: https://orcid.org/0000-0001-7206-8088)
- Carmen R. Isasi (ORCID: https://orcid.org/0000-0003-2700-9593)
- Tanika N. Kelly (ORCID: https://orcid.org/0000-0002-7348-4451)
- Mariaelisa Graff (ORCID: https://orcid.org/0000-0001-6380-1735)
- Kari E. North (ORCID: https://orcid.org/0000-0002-8903-0366)
- Linda C. Gallo (ORCID: https://orcid.org/0000-0002-3678-5888)
- Lindsay Fernández‐Rhodes (ORCID: https://orcid.org/0000-0001-6985-423X)
- Martha L. Daviglus (ORCID: https://orcid.org/0000-0002-6791-8727)
- Jayati Sharma (ORCID: https://orcid.org/0000-0002-4084-8319)
- Jianwen Cai (ORCID: https://orcid.org/0000-0002-4945-6733)
Institutions
- University of North Carolina at Chapel Hill (US)
- Albert Einstein College of Medicine (US)
- Pennsylvania State University (US)
- Johns Hopkins University (US)
- University of Miami (US)
- San Diego State University (US)
- University of Illinois Chicago (US)
Publication Details
- Journal
- Human Genetics and Genomics Advances
- Published
- 2025-05-08
- DOI
- https://doi.org/10.1016/j.xhgg.2025.100451
- Citations
- 2
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 3.63
Funders
- Office of Dietary Supplements
- University of Miami
- San Diego State University
- Albert Einstein College of Medicine, Yeshiva University
- University of Illinois at Chicago
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute
- National Institute on Deafness and Other Communication Disorders
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute of Dental and Craniofacial Research
- National Institute on Minority Health and Health Disparities
- NHLBI Division of Intramural Research