title: Physical activity and genetic predisposition to obesity in a multiethnic longitudinal study.
abstract: Physical activity (PA) has been shown to reduce the impact of FTO variation and obesity genetic risk scores (GRS) on BMI. We examined this interaction using a quantitative measure of PA and two adiposity indexes in a longitudinal multi-ethnic study. We analyzed the impact of PA on the association between 14 obesity predisposing variants (analyzed independently and as a GRS) and baseline/follow-up obesity measures in the multi-ethnic prospective cohort EpiDREAM (17423 participants from six ethnic groups). PA was analyzed using basic (low-moderate-high) and quantitative measures (metabolic equivalents (METS)), while BMI and the body adiposity index (BAI) were used to measure obesity. Increased PA was associated with decreased BMI/BAI at baseline/follow-up. FTO rs1421085, CDKAL1 rs2206734, TNNl3K rs1514176, GIPR rs11671664 and the GRS were associated with obesity measures at baseline and/or follow-up. Risk alleles of three SNPs displayed nominal associations with increased (NTRK2 rs1211166, BDNF rs1401635) or decreased (NPC1 rs1805081) basic PA score independently of BMI/BAI. Both basic and quantitative PA measures attenuated the association between FTO rs1421085 risk allele and BMI/BAI at baseline and follow-up. Our results show that physical activity can blunt the genetic effect of FTO rs1421085 on adiposity by 36-75% in a longitudinal multi-ethnic cohort.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Hudson
authors.initials: H
authors.lastname: Reddon
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.affiliation: Departments of Medicine and Human Genetics, McGill University, Montreal, QC, Canada.
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
authors.affiliation: Madras Diabetes Research Foundation, Chennai, India.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.affiliation: Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada.
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada.
authors.forename: Dipika
authors.initials: D
authors.lastname: Desai
authors.affiliation: Departments of Medicine and Human Genetics, McGill University, Montreal, QC, Canada.
authors.forename: Swneke D
authors.initials: SD
authors.lastname: Bailey
authors.affiliation: ECLA-Academic Research Organization, Rosario, Argentina.
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada.|Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Sonia S
authors.initials: SS
authors.lastname: Anand
authors.affiliation: Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada.|Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario, Canada.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Meyre
mesh_terms: D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics*; D063868:Patient Outcome Assessment; D020641:Polymorphism, Single Nucleotide; D012306:Risk