Gene-Environment Interactions and Gene-Gene Interactions on Two Biological Age Measures: Evidence from Taiwan Biobank Participants.

Abstract

PhenoAge and BioAge are two commonly used biological age (BA) measures. The author here searched for gene-environment interactions (GxE) and gene-gene interactions (GxG) on PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 111,996 Taiwan Biobank (TWB) participants, including a discovery set of 86,536 TWB2 individuals and a replication set of 25,460 TWB1 individuals. Searching for variance quantitative trait loci (vQTLs) provides a convenient way to evaluate GxE and GxG. A total of 4 nearly independent (linkage disequilibrium measure r2 < 0.01) PhenoAgeAccel-vQTLs are identified from 5,303,039 autosomal TWB2 SNPs (p < 5E-8), whereas no vQTLs are found from BioAgeAccel. These 4 PhenoAgeAccel-vQTLs (rs35276921, rs141927875, rs10903013, and rs76038336) are further replicated by TWB1 (p < 5E-8). They are located in the OR51B5, FAM234A, and AXIN1 genes. All 4 PhenoAgeAccel-vQTLs are significantly associated with PhenoAgeAccel (p < 5E-8). A phylogenetic heat map of the GxE analyses showed that smoking exacerbated the PhenoAgeAccel-vQTLs' aging effects, while higher educational attainment attenuated the PhenoAgeAccel-vQTLs' aging effects. Body mass index, chronological age, alcohol consumption, and sex do not prominently modulate PhenoAgeAccel-vQTLs' aging effects. Based on these vQTL results, rs141927875-rs35276921 interaction (p = 4.7E-61) and rs76038336-rs10903013 interaction (p = 3.3E-116) on PhenoAgeAccel are detected.