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

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

BMC Medical Genomics, December 2015

26683835

Shafqat Ahmad, Wei Zhao, Frida Renström, Asif Rasheed, Maria Samuel, Mozzam Zaidi, Nabi Shah, Nadeem Hayyat Mallick, Khan Shah Zaman, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-ur-Rheman Memon, Bashir Hanif, Muhammad Shakir Lakhani, Faisal Ahmed, Shahana Urooj Kazmi, Philippe Frossard, Paul W. Franks, Danish Saleheen

Multiple 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. In 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, age(2), sex, MI (yes/no), and population substructure. Of 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/m(2) higher BMI (P = 4.5 × 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P interaction = 0.014), CADM2 rs13078960 (P interaction = 0.037) and GALNT10 rs7715256 (P interaction = 0.048) with physical activity, and PTBP2 rs11165643 (P interaction = 0.045), HIP1 rs1167827 (P interaction = 0.015), C6orf106 rs205262 (P interaction = 0.032) and GRID1 rs7899106 (P interaction = 0.043) with smoking on BMI. Most 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.