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

Publication

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

Journal Paper/Review - Dec 18, 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

Citation

Ahmad S, Franks P, Frossard P, Kazmi S, Ahmed F, Lakhani M, Hanif B, Memon F, Rasheed S, Ishaq M, Zaman K, Mallick N, Shah N, Zaidi M, Samuel M, Rasheed A, Renström F, Zhao W, Saleheen D. Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study. BMC Med Genet 2015; 16:114.

Type

Journal Paper/Review (English)

Journal

BMC Med Genet 2015; 16

Publication Date

Dec 18, 2015

Issn Electronic

1471-2350

Pages

114

Brief description/objective

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.