Gene‐Environment Interactions and Gene–Gene Interactions on Two Biological Age Measures: Evidence from Taiwan Biobank Participants

Abstract

AbstractPhenoAge 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.