Bridging the genetic gap: a gene-environment analysis of social bridging, APOE genotype, and cognitive health

• In Event: Advances in Social Science Genomics (Co-sponsored by Sociology of Population Section)

Abstract

The rising prevalence of Alzheimer’s disease and related dementias (ADRD) underscores an urgent need to identify modifiable life-course factors that mitigate biological vulnerability. While the APOE ε4 allele is the most known genetic risk factor for ADRD, its impact is not deterministic. Drawing on a biosocial Gene–Environment (GxE) framework, this study investigates whether bridging social capital—characterized by structurally diverse and expansive social networks—buffers the cognitive disadvantages associated with genetic risk.
We utilize data from the Social Networks in Alzheimer’s Disease (SNAD) study (N=378) and the nationally representative Health and Retirement Study (HRS) (N=8,976). To address the "methodological gap" in large-scale datasets, we construct and validate a latent network diversity proxy to operationalize bridging. In the high-resolution SNAD sample, this proxy demonstrates strong concurrent validity with a full egocentric bridging measure (r=0.667, p<.001). Cognitive function is assessed via the MoCA (SNAD) and TICS (HRS), and APOE genotype is categorized into non-carriers, heterozygotes, and homozygotes.
Across both samples, bridging/network diversity is positively associated with cognitive performance, while APOE ε4—especially homozygosity—is associated with lower cognitive scores. Critically, we observe a consistent G×E interaction: higher social bridging or network diversity significantly attenuates the cognitive disadvantage among ε4 homozygotes. Individuals at highest genetic risk derive the greatest cognitive benefit from structurally diverse networks, effectively narrowing the cognitive gap with non-carriers. This buffering pattern replicates in the population-level HRS sample.
These findings advance a biosocial model of cognitive resilience, demonstrating that relational social environments condition the expression of genetic vulnerability. Methodologically, the validated network diversity proxy enables scalable replication of theoretically grounded bridging measures in large surveys. Substantively, the results underscore that genetic risk for cognitive decline is socially embedded and potentially modifiable through structurally diverse social engagement.

Authors

• Wenhua (Zoey) Lai, Wayne State University

• Tianyao Qu, Indiana University-Bloomington

• Siyun Peng, Indiana University-Bloomington

• Brea Louise Perry, Indiana University-Bloomington