TY - JOUR
T1 - Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan
T2 - the PROMIS study
AU - Ahmad, Shafqat
AU - Zhao, Wei
AU - Renström, Frida
AU - Rasheed, Asif
AU - Samuel, Maria
AU - Zaidi, Mozzam
AU - Shah, Nabi
AU - Mallick, Nadeem Hayyat
AU - Zaman, Khan Shah
AU - Ishaq, Mohammad
AU - Rasheed, Syed Zahed
AU - Memon, Fazal ur Rheman
AU - Hanif, Bashir
AU - Lakhani, Muhammad Shakir
AU - Ahmed, Faisal
AU - Kazmi, Shahana Urooj
AU - Frossard, Philippe
AU - Franks, Paul W.
AU - Saleheen, Danish
PY - 2015/12/18
Y1 - 2015/12/18
N2 - 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, age2, 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/m2 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.
AB - 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, age2, 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/m2 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.
KW - Gene-lifestyle interactions
KW - Genetic susceptibility
KW - Obesity
KW - Physical activity
KW - Smoking
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U2 - 10.1186/s12881-015-0259-x
DO - 10.1186/s12881-015-0259-x
M3 - Article
AN - SCOPUS:84949948863
VL - 16
JO - BMC Medical Genetics
JF - BMC Medical Genetics
SN - 1471-2350
IS - 1
M1 - 114
ER -