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

Abstract

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.

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease

“…Because BSN is universally expressed in neurons, we combined expression data across all eight neuronal clusters in the differential gene expression analysis and performed pathway enrichment analyses to examine the possible global consequences of BSN +/− . Differential expression analyses revealed 778 genes (defined by P < 0.05 and log 2 (fold change (FC)) > 1 or < −1) (Supplementary Table 12 ), including downregulation of genes with reported roles in body weight regulation, such as SEMA3C 25 and APOE 26 , 27 . The top enriched pathways included ‘neuroactive ligand-receptor interaction’ and ‘negative regulation of neurogenesis’, as well as ‘respiratory chain complex I (gamma subunit) mitochondrial’.…”

Biomarkers of Aging and Relevant Evaluation Techniques: A Comprehensive Review

“…To identify GVs that show differential effects on age-dependent obesity, Ju et al conducted a GWAS on 355,335 UK Biobank participants, stratified the analysis of five obesity-related phenotypes, and conducted t-statistics. Five significant lead SNPs were identified: rs9861311 and rs429358 for body fat percentage, rs2258461 for body mass index, rs145500243 for waist circumference, and rs2870099 for waist-to-hip ratio [ 56 ]. Notably, rs429358, located in APOE, is also associated with various age-related diseases such as cognitive decline, coronary artery disease, and age-related macular disease [ 57 , 58 ].…”

Prevalence and impact of a protein-truncating POMC variant on obesity in the Estonian Biobank

“…We acquired adult body-mass index values for 204,747 EstBB participants from electronic health records (EHRs) and self-reported questionnaires [18][19][20] . As EstBB contains multiple BMI values per participant, we used the earliest possible measurement (Supplementary Figure 1), since genetic effects on body weight are more likely to manifest at an early adulthood age 21,22 .…”