title: Life-course analysis of a fat mass and obesity-associated (FTO) gene variant and body mass index in the Northern Finland Birth Cohort 1966 using structural equation modeling.
abstract: The association between variation in the fat mass and obesity-associated (FTO) gene and adulthood body mass index (BMI; weight (kg)/height (m)(2)) is well-replicated. More thorough analyses utilizing phenotypic data over the life course may deepen our understanding of the development of BMI and thus help in the prevention of obesity. The authors used a structural equation modeling approach to explore the network of variables associated with BMI from the prenatal period to age 31 years (1965-1997) in 4,435 subjects from the Northern Finland Birth Cohort 1966. The use of structural equation modeling permitted the easy inclusion of variables with missing values in the analyses without separate imputation steps, as well as differentiation between direct and indirect effects. There was an association between the FTO single nucleotide polymorphism rs9939609 and BMI at age 31 years that persisted after controlling for several relevant factors during the life course. The total effect of the FTO variant on adult BMI was mostly composed of the direct effect, but a notable part was also arising indirectly via its effects on earlier BMI development. In addition to well-established genetic determinants, many life-course factors such as physical activity, in spite of not showing mediation or interaction, had a strong independent effect on BMI.
authors: Institute of Health Sciences, Faculty of Medicine, University of Oulu, Oulu, Finland.
authors: Marika
authors: M
authors: Kaakinen
authors: Esa
authors: E
authors: Läärä
authors: Anneli
authors: A
authors: Pouta
authors: Anna-Liisa
authors: AL
authors: Hartikainen
authors: Jaana
authors: J
authors: Laitinen
authors: Tuija H
authors: TH
authors: Tammelin
authors: Karl-Heinz
authors: KH
authors: Herzig
authors: Ulla
authors: U
authors: Sovio
authors: Amanda J
authors: AJ
authors: Bennett
authors: Leena
authors: L
authors: Peltonen
authors: Mark I
authors: MI
authors: McCarthy
authors: Paul
authors: P
authors: Elliott
authors: Bianca
authors: B
authors: De Stavola
authors: Marjo-Riitta
authors: MR
authors: Järvelin
mesh_terms: D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D001110:Arctic Regions; D015992:Body Mass Index; D004032:Diet; D015444:Exercise; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008297:Male; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D012907:Smoking; D012959:Socioeconomic Factors
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human