Sharma Jayati, McArdle Cristin E, Graff Mariaelisa, Cordero Christina, Daviglus Martha, Gallo Linda C, Isasi Carmen R, Kelly Tanika N, Perreira Krista M, Talavera Gregory A, Cai Jianwen, North Kari E, Fernández-Rhodes Lindsay, Wojcik Genevieve L
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Department of Biobehavioral Health, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA.
HGG Adv. 2025 May 8;6(3):100451. doi: 10.1016/j.xhgg.2025.100451.
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). 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 and other health-related variables. Interaction effects were modeled between PGS 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 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.
通常情况下，研究往往会将所有被认定为西班牙裔/拉丁裔的参与者归为一类，而忽略了其遗传和环境亚结构，从而无法对遗传因素和环境因素在人类健康中的作用进行有意义的探究。我们利用西班牙裔社区健康研究/拉丁裔研究（HCHS/SOL），研究了自我认定的背景群体和遗传血统如何影响体重指数（BMI）与BMI多基因评分（PGS）之间的基因-环境相互作用。参与者（n = 7,075）被分为六个背景群体：中美洲、古巴、多米尼加、墨西哥、波多黎各和南美洲。采用纳入复杂调查权重的广义线性模型，通过联合分析和分层分析（背景群体、估计的美洲原住民[AME]血统）对BMI进行建模，分析内容包括PGS和其他健康相关变量。对PGS与饮食以及移民年龄之间的相互作用效应进行了建模。与合并分析相比，背景群体分层分析显示，环境和社会文化变量的分布存在异质性，与AME血统的关联也有所不同。在多变量模型中，PGS的表现随着AME血统的增加而下降。分层后，PGS与移民年龄之间的相互作用在某些分层中仍具有统计学意义：在美国（50个州/哥伦比亚特区）出生的墨西哥背景个体（β = 1.33，p < 0.01）、6至12岁的多米尼加背景个体（β = 4.38，p < 0.001）以及0至5岁的古巴背景个体（β = 2.20，p = 0.015）相对于移民时年龄≥21岁的个体。为了对感兴趣的人群进行适当建模并防止可能的混杂或误解，了解这些人群至关重要。虽然这项工作专门针对西班牙裔/拉丁裔群体，但随着我们开展多样化研究以更好地理解基因-环境相互作用，这些经验教训对其他群体也具有借鉴意义。
