title: Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study.
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.
authors.affiliation: Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden. shafqat.ahmad@med.lu.se.
authors.forename: Shafqat
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. zhaowei1@mail.med.upenn.edu.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden. frida.renstrom@med.lu.se.
authors.forename: Frida
authors.initials: F
authors.lastname: Renström
authors.affiliation: Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan. asif.rasheed@cncdpk.com.
authors.forename: Asif
authors.initials: A
authors.lastname: Rasheed
authors.affiliation: Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan. marry.samuel@yahoo.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Samuel
authors.affiliation: Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan. drmoazzam_2003@yahoo.com.
authors.forename: Mozzam
authors.initials: M
authors.lastname: Zaidi
authors.affiliation: Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan. nabi.shah@yahoo.co.uk.|Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan. nabi.shah@yahoo.co.uk.
authors.forename: Nabi
authors.initials: N
authors.lastname: Shah
authors.affiliation: Punjab Institute of Cardiology, Lahore, Pakistan. nhmallick@hotmail.com.
authors.forename: Nadeem Hayyat
authors.initials: NH
authors.lastname: Mallick
authors.affiliation: National Institute of Cardiovascular Diseases, Karachi, Pakistan. zamanfhc@yahoo.com.
authors.forename: Khan Shah
authors.initials: KS
authors.lastname: Zaman
authors.affiliation: Karachi Institute of Heart Diseases, Karachi, Pakistan. khyber50@yahoo.com.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ishaq
authors.affiliation: Karachi Institute of Heart Diseases, Karachi, Pakistan. szrasheed@yahoo.com.
authors.forename: Syed Zahed
authors.initials: SZ
authors.lastname: Rasheed
authors.affiliation: Red Crescent Institute of Cardiology, Hyderabad, Karachi, Pakistan. frmemon@yahoo.com.
authors.forename: Fazal-ur-Rheman
authors.initials: FU
authors.lastname: Memon
authors.affiliation: Tabba Heart Institute, Karachi, Pakistan. bashir.hanif@tabbaheart.org.
authors.forename: Bashir
authors.initials: B
authors.lastname: Hanif
authors.affiliation: Tabba Heart Institute, Karachi, Pakistan. muhammad.lakhani@tabbaheart.org.
authors.forename: Muhammad Shakir
authors.initials: MS
authors.lastname: Lakhani
authors.affiliation: Department of Cardiology, Liaquat National Hospital, Karachi, Pakistan. faisal.ahmed@lnh.edu.pk.
authors.forename: Faisal
authors.initials: F
authors.lastname: Ahmed
authors.affiliation: Department of Microbiology, University of Karachi, Karachi, Pakistan. shahanaurooj@yahoo.com.
authors.forename: Shahana Urooj
authors.initials: SU
authors.lastname: Kazmi
authors.affiliation: Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan. philippe.frossard@cncdpk.com.|Nazarbayev University, Astana, Kazakhstan. philippe.frossard@cncdpk.com.
authors.forename: Philippe
authors.initials: P
authors.lastname: Frossard
authors.affiliation: Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden. paul.franks@med.lu.se.|Department of Public Health and Clinical Medicine, Section for Medicine, Umeå University, Umeå, Sweden. paul.franks@med.lu.se.|Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. paul.franks@med.lu.se.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. saleheen@mail.med.upenn.edu.|Center for Non-Communicable Diseases Pakistan, Karachi, Pakistan. saleheen@mail.med.upenn.edu.|Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, USA. saleheen@mail.med.upenn.edu.
authors.forename: Danish
authors.initials: D
authors.lastname: Saleheen
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D016017:Odds Ratio; D010154:Pakistan; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000503:physiopathology*