TY - JOUR
T1 - Genetic ancestry influences gene-environment interactions with sociocultural factors
T2 - Results from the Hispanic Community Health Study/Study of Latinos
AU - Sharma, Jayati
AU - McArdle, Cristin E.
AU - Graff, Mariaelisa
AU - Cordero, Christina
AU - Daviglus, Martha
AU - Gallo, Linda C.
AU - Isasi, Carmen R.
AU - Kelly, Tanika N.
AU - Perreira, Krista M.
AU - Talavera, Gregory A.
AU - Cai, Jianwen
AU - North, Kari E.
AU - Fernández-Rhodes, Lindsay
AU - Wojcik, Genevieve L.
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/7/10
Y1 - 2025/7/10
N2 - 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 (PGSBMI). 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 PGSBMI and other health-related variables. Interaction effects were modeled between PGSBMI 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, PGSBMI 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.
AB - 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 (PGSBMI). 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 PGSBMI and other health-related variables. Interaction effects were modeled between PGSBMI 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, PGSBMI 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.
UR - https://www.scopus.com/pages/publications/105005960934
UR - https://www.scopus.com/pages/publications/105005960934#tab=citedBy
U2 - 10.1016/j.xhgg.2025.100451
DO - 10.1016/j.xhgg.2025.100451
M3 - Article
C2 - 40340254
AN - SCOPUS:105005960934
SN - 2666-2477
VL - 6
JO - Human Genetics and Genomics Advances
JF - Human Genetics and Genomics Advances
IS - 3
M1 - 100451
ER -
