GWAS of habitual coffee consumption reveals a sex difference in the genetic effect of the 12q24 locus in the Japanese population

Abstract

Abstract Background Studies on genetic effects of coffee consumption are scarce for Asian populations. We conducted a genome-wide association study (GWAS) of habitual coffee consumption in Japan using a self-reporting online survey. Results Candidate genetic loci associated with habitual coffee consumption were searched within a discovery cohort (N = 6,264) and confirmed in a replication cohort (N = 5,975). Two loci achieved genome-wide significance (P < 5 × 10− 8) in a meta-analysis of the discovery and replication cohorts: an Asian population-specific 12q24 (rs79105258; P = 9.5 × 10− 15), which harbors CUX2, and 7p21 (rs10252701; P = 1.0 × 10− 14), in the upstream region of the aryl hydrocarbon receptor (AHR) gene, involved in caffeine metabolism. Subgroup analysis revealed a stronger genetic effect of the 12q24 locus in males (P for interaction = 8.2 × 10− 5). Further, rs79105258 at the 12q24 locus exerted pleiotropic effects on body mass index (P = 3.5 × 10− 4) and serum triglyceride levels (P = 8.7 × 10− 3). Conclusions Our results consolidate the association of habitual coffee consumption with the 12q24 and 7p21 loci. The different effects of the 12q24 locus between males and females are a novel finding that improves our understanding of genetic influences on habitual coffee consumption.

Keywords

• 12q24 locus
• AHR
• Coffee consumption
• East Asians
• Genome-wide association study