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.
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.
Kaakinen
Marika
M
Institute of Health Sciences, Faculty of Medicine, University of Oulu, Oulu, Finland.
Läärä
Esa
E
Pouta
Anneli
A
Hartikainen
Anna-Liisa
AL
Laitinen
Jaana
J
Tammelin
Tuija H
TH
Herzig
Karl-Heinz
KH
Sovio
Ulla
U
Bennett
Amanda J
AJ
Peltonen
Leena
L
McCarthy
Mark I
MI
Elliott
Paul
P
De Stavola
Bianca
B
Järvelin
Marjo-Riitta
MR
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
D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human