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Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the interactions of the HDL-C-related SNPs with PA on HDL-C. The sex-stratified GWA analyses identified 11 and 10 HDL-C-related SNPs in men and women as targets for an interaction analysis. Among these, only one interaction of ABCA1 rs1883025 with PA was statistically significant in men, after Bonferroni correction [P-interaction = 0.001 (α = 0.05/21 = 0.002)]. The per-major-allele (C allele) increase in log-transformed HDL-C was lost in men with low PA (β = 0.008) compared with those with medium (β = 0.032) or high PA (β = 0.034). These findings suggest that the benefit of carrying a C allele of ABCA1 rs1883025 on enhancing HDL-C may be attenuated in inactive men.

The purpose of the study was to investigate sex-specific associations of skipping breakfast and short sleep duration with metabolic syndrome (MetS) and their interaction. We analyzed baseline data of 14,907 men and 14,873 women aged 35–69 years, who participated in the Japan Multi-Institutional Collaborative Cohort Study from 2005. MetS was diagnosed using a modification of the National Cholesterol Education Program Adult Treatment Panel III revised definition (NCEP-R 2005), using body mass index instead of waist circumference. Breakfast consumption was classified into two categories: ≥6 days/week (consumers) or