Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study

Abstract

BackgroundMultiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians.MethodsIn 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age2, sex, MI (yes/no), and population substructure.ResultsOf 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m2 higher BMI (P = 4.5 × 10−14). We observed nominal evidence of interactions of CLIP1 rs11583200 (Pinteraction = 0.014), CADM2 rs13078960 (Pinteraction = 0.037) and GALNT10 rs7715256 (Pinteraction = 0.048) with physical activity, and PTBP2 rs11165643 (Pinteraction = 0.045), HIP1 rs1167827 (Pinteraction = 0.015), C6orf106 rs205262 (Pinteraction = 0.032) and GRID1 rs7899106 (Pinteraction = 0.043) with smoking on BMI.ConclusionsMost BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-015-0259-x) contains supplementary material, which is available to authorized users.

The importance of gene–environment interactions in human obesity

“…A number of gene × smoking interactions were identified when African Americans and Caucasians were analysed separately, but no significant interactions were observed in the overall sample from the Southern Community Cohort Study [167]. Four nominally significant gene × smoking interactions were reported in a recent study of 16157 Pakistani adults, with current smoking status amplifying the effect of PTBP2 rs11165643, HIP1 rs1167827 and GRID1 rs7899106 SNPs, and decreasing the effect of C6orf106 rs205262 SNP [120].…”

Sexual Dimorphism of a Genetic Risk Score for Obesity and Related Traits among Chinese Patients with Type 2 Diabetes

“…Gene-environment interaction plays an essential role in the determinant of complex trait/disease. For example, several studies have indicated that the estimated effective size of the risk alleles for obesity is more pronounced in smokers and individuals with a low physical activity [40-42]. In the Chinese population, lifestyle factors (such as smoking and less physical activity, etc.)…”

A global evolutionary and metabolic analysis of human obesity gene risk variants

“…These GWAS and subsequent transferability studies performed in diverse populations from around the world have identified gene risk variants associated with human obesity (Hester et al, 2012; Ahmad et al, 2015; Hagg et al, 2015; Locke et al, 2015; Abadi et al, 2016). The sample data consists of 110 human obesity genes (56 obesity genes with ancestral risk variants and 54 obesity genes with derived risk variants).…”

“…To determine the molecular basis of common obesity that has reached epidemic proportions in the United States and other developed countries, a large number of genome-wide association studies (GWAS) have been performed to identify obesity gene risk variants that increase susceptibility to this metabolic disease (Meyre et al, 2009; Thorleifsson et al, 2009; Willer et al, 2009; Scherag et al, 2010; Speliotes et al, 2010; Kilpelainen et al, 2011; Bradfield et al, 2012; Wen et al, 2012; Berndt et al, 2013; Bian et al, 2013; Monda et al, 2013; Locke et al, 2015; Minster et al, 2016). These GWAS and subsequent transferability studies performed in different populations around the world have now validated 110 human obesity genes with 127 nearest obesity gene risk variants (Hester et al, 2012; Ahmad et al, 2015; Hagg et al, 2015; Locke et al, 2015; Abadi et al, 2016). It is generally accepted that the obesity epidemic is a recent manifestation that has occurred during the past few decades and not all individuals or populations are adversely affected, thereby suggesting individual differences based on genetic variability and interactions with an obesogenic environment (Nakamura et al, 2015; Nettleton et al, 2015; Reddon et al, 2016).…”