Identification of five genetic variants with differential effects on obesity-related traits based on age

Obesity is a major public health concern, and its prevalence generally increases with age. As the number of elderly people is increasing in the aging population, the age-dependent increase in obesity has raised interest in the underlying mechanism. To understand the genetic basis of age-related increase in obesity, we identified genetic variants showing age-dependent differential effects on obesity. We conducted stratified analyses between young and old groups using genome-wide association studies of 355,335 United Kingom Biobank participants for five obesity-related phenotypes, including body mass index, body fat percentage, waist-hip ratio, waist circumference, and hip circumference. Using t-statistic, we identified five significant lead single nucleotide polymorphisms: rs2258461 with body mass index, rs9861311 and rs429358 with body fat percentage, rs2870099 with waist-hip ratio, and rs145500243 with waist circumference. Among these single nucleotide polymorphisms, rs429358, located in APOE gene was associated with diverse age-related diseases, such as Alzheimer's disease, coronary artery disease, age-related degenerative macular diseases, and cognitive decline. The C allele of rs429358 gradually decreases body fat percentage as one grows older in the range of 40-69 years. In conclusion, we identified five genetic variants with differential effects on obesity-related phenotypes based on age using a stratified analysis between young and old groups, which may help to elucidate the mechanisms by which age influences the development of obesity.