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
Author(s)
Type
Journal Article
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.
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.
Date Issued
2010-09-15
Date Acceptance
2010-05-17
Citation
American Journal of Epidemiology, 2010, 172 (6), pp.653-665
ISSN
1476-6256
Publisher
Oxford University Press (OUP)
Start Page
653
End Page
665
Journal / Book Title
American Journal of Epidemiology
Volume
172
Issue
6
Copyright Statement
© The Author 2010. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial
License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use,
distribution, and reproduction in any medium, provided the original work is properly cited.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial
License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use,
distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Public, Environmental & Occupational Health
PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH, SCI
body mass index
molecular epidemiology
structural equation model
GENOME-WIDE ASSOCIATION
AGE 31 YEARS
PHYSICAL-ACTIVITY
ADULT OBESITY
EUROPEAN POPULATIONS
METABOLIC SYNDROME
BLOOD-PRESSURE
ENERGY-INTAKE
FIT INDEXES
TRAITS
Publication Status
Published