Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan

the PROMIS study

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-Rehman Memon, Bashir Hanif, Muhammad Shakir Lakhani, S. Faisal Ahmed, Shahana Urooj Kazmi, Philippe Frossard, Paul W. Franks (Lead / Corresponding author), Danish Saleheen (Lead / Corresponding author)

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Abstract

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.
Original languageEnglish
Article number114
Pages (from-to)1-11
Number of pages11
JournalBMC Medical Genetics
Volume16
DOIs
Publication statusPublished - 18 Dec 2015

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Pakistan
Genetic Predisposition to Disease
Obesity
Smoking
Exercise
Single Nucleotide Polymorphism
Myocardial Infarction
Life Style
Alleles
Population

Keywords

  • Obesity
  • Physical activity
  • Smoking
  • Genetic susceptibility
  • Gene-lifestyle interactions

Cite this

Ahmad, S., Zhao, W., Renström, F., Rasheed, A., Samuel, M., Zaidi, M., ... Saleheen, D. (2015). Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study. BMC Medical Genetics, 16, 1-11. [114]. https://doi.org/10.1186/s12881-015-0259-x
Ahmad, Shafqat ; Zhao, Wei ; Renström, Frida ; Rasheed, Asif ; Samuel, Maria ; Zaidi, Mozzam ; Shah, Nabi ; Mallick, Nadeem Hayyat ; Zaman, Khan Shah ; Ishaq, Mohammad ; Rasheed, Syed Zahed ; Memon, Fazal-ur-Rehman ; Hanif, Bashir ; Lakhani, Muhammad Shakir ; Ahmed, S. Faisal ; Kazmi, Shahana Urooj ; Frossard, Philippe ; Franks, Paul W. ; Saleheen, Danish. / Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan : the PROMIS study. In: BMC Medical Genetics. 2015 ; Vol. 16. pp. 1-11.
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abstract = "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.",
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author = "Shafqat Ahmad and Wei Zhao and Frida Renstr{\"o}m and Asif Rasheed and Maria Samuel and Mozzam Zaidi and Nabi Shah and Mallick, {Nadeem Hayyat} and Zaman, {Khan Shah} and Mohammad Ishaq and Rasheed, {Syed Zahed} and Fazal-ur-Rehman Memon and Bashir Hanif and Lakhani, {Muhammad Shakir} and Ahmed, {S. Faisal} and Kazmi, {Shahana Urooj} and Philippe Frossard and Franks, {Paul W.} and Danish Saleheen",
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Ahmad, S, Zhao, W, Renström, F, Rasheed, A, Samuel, M, Zaidi, M, Shah, N, Mallick, NH, Zaman, KS, Ishaq, M, Rasheed, SZ, Memon, F-R, Hanif, B, Lakhani, MS, Ahmed, SF, Kazmi, SU, Frossard, P, Franks, PW & Saleheen, D 2015, 'Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study', BMC Medical Genetics, vol. 16, 114, pp. 1-11. https://doi.org/10.1186/s12881-015-0259-x

Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan : the PROMIS study. / Ahmad, Shafqat; Zhao, Wei; Renström, Frida; Rasheed, Asif; Samuel, Maria; Zaidi, Mozzam; Shah, Nabi; Mallick, Nadeem Hayyat; Zaman, Khan Shah; Ishaq, Mohammad; Rasheed, Syed Zahed; Memon, Fazal-ur-Rehman ; Hanif, Bashir; Lakhani, Muhammad Shakir; Ahmed, S. Faisal; Kazmi, Shahana Urooj; Frossard, Philippe; Franks, Paul W. (Lead / Corresponding author); Saleheen, Danish (Lead / Corresponding author).

In: BMC Medical Genetics, Vol. 16, 114, 18.12.2015, p. 1-11.

Research output: Contribution to journalArticle

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-Rehman

AU - Hanif, Bashir

AU - Lakhani, Muhammad Shakir

AU - Ahmed, S. 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, 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.

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, 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.

KW - Obesity

KW - Physical activity

KW - Smoking

KW - Genetic susceptibility

KW - Gene-lifestyle interactions

U2 - 10.1186/s12881-015-0259-x

DO - 10.1186/s12881-015-0259-x

M3 - Article

VL - 16

SP - 1

EP - 11

JO - BMC Medical Genetics

JF - BMC Medical Genetics

SN - 1471-2350

M1 - 114

ER -