Publikation
Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study
Wissenschaftlicher Artikel/Review - 18.12.2015
Ahmad Shafqat, Franks Paul W, Frossard Philippe, Kazmi Shahana Urooj, Ahmed Faisal, Lakhani Muhammad Shakir, Hanif Bashir, Memon Fazal-ur-Rheman, Rasheed Syed Zahed, Ishaq Mohammad, Zaman Khan Shah, Mallick Nadeem Hayyat, Shah Nabi, Zaidi Mozzam, Samuel Maria, Rasheed Asif, Renström Frida, Zhao Wei, Saleheen Danish
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BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.