Genetic Ancestry and Gene-environment Interactions in a Hispanic/Latino Cohort

Drs. Sharma and Wojcik will present recently published work investigating the role of both genetic ancestry and sociocultural factors when considering the genetic risk for body-mass-index (BMI) in the Hispanic Community Health Study/Study of Latinos. Significant gene-environment interactions persisted in only some subgroups of Hispanic/Latino ethnicity, even after adjustment for ancestry differences, emphasizing the importance of finer-level population descriptors in avoiding spurious findings of gene-environment interactions due to both genetic and sociocultural substructure.

Overview of Presentation:

• We conducted an analysis of over 7,000 participants in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) to examine how self-identified background group and genetic ancestry influence gene–environment interactions between BMI and a polygenic score for BMI (PGSBMI).
• We found that pooled analyses masked important heterogeneity—environmental and sociocultural variables, as well as genetic ancestry (particularly Amerindigenous [AME] ancestry), varied significantly across background groups.
• The predictive performance of the BMI polygenic score decreased with increasing AME ancestry, and significant gene–environment interactions with age at immigration persisted in certain subgroups.
• Disaggregating analyses by both background group and genetic ancestry is critical to avoid confounding and misinterpretation of gene-environment interactions in a Hispanic/Latino cohort.
• The equitable application of precision medicine tools requires finer detail on population descriptors in large, diverse study populations to better characterize important genetic and environmental heterogeneity within and between groups.