Dataset Information

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.

SUBMITTER: Kaakinen M

PROVIDER: S-EPMC2938267 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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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.

Kaakinen Marika M 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

American journal of epidemiology 20100811 6

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 ...[more]

PMID: 20702506

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Project description:BackgroundThe CHRNA5-CHRNA3-CHRNB4 gene cluster on 15q25 has consistently been associated with smoking quantity, nicotine dependence and lung cancer. Recent research also points towards its involvement in cardiovascular homeostasis, but studies in large human samples are lacking, especially on the role of the gene cluster in blood pressure regulation.Methodology/principal findingsWe studied the associations between 18 single nucleotide polymorphisms (SNPs) in CHRNA5-CHRNA3-CHRNB4 and systolic blood pressure (SBP), diastolic blood pressure (DBP), and body mass index (BMI) in 5402 young adults from the Northern Finland Birth Cohort 1966. We observed some evidence for associations between two SNPs and SBP and between six SNPs and BMI; the evidence for associations with DBP was weaker. The associations with the three phenotypes were driven by different loci with low linkage disequilibrium with each other. The associations appeared more pronounced in smokers, such that the smoking-increasing alleles would predict lower SBP and BMI. Each additional copy of the rs1948 G-allele and the rs950776 A-allele reduced SBP on average by -1.21 (95% CI -2.01, -0.40) mmHg in smokers. The variants associated with BMI included rs2036534, rs6495309, rs1996371, rs6495314, rs4887077 and rs11638372 and had an average effect size of -0.38 (-0.68, -0.08) kg/m(2) per an additional copy of the risk allele in smokers. Formal assessments of interactions provided weaker support for these findings, especially after adjustment for multiple testing.ConclusionsVariation at 15q25 appears to interact with smoking status in influencing SBP and BMI. The genetic loci associated with SBP were in low linkage disequilibrium with those associated with BMI suggesting that the gene cluster might regulate SBP through biological mechanisms that partly differ from those regulating BMI. Further studies in larger samples are needed for more precise evaluation of the possible interactions, and to understand the mechanisms behind.

Project description:BackgroundThe effect of urban sprawl on body weight in Finland is not well known. To provide more information, we examined whether body mass index (BMI) and the prevalence of overweight are associated with an individual's distance to the local community centre and population density in his/her resident area.MethodsThe sample consisted of 5363 men and women, members of the Northern Finland Birth Cohort 1966 (NFBC), who filled in a postal questionnaire and attended a medical checkup in 1997, at the age of 31 years. Body mass index (BMI; kg/m(2)) and the prevalence of overweight (BMI ? 25.0 kg/m(2)) were regressed on each subject's road distance to the resident commune's centre and on population density in the 1 km(2) geographical grid in which he/she resided, using a generalized additive model. Adjustments were made for sex, marital status, occupational class, education, leisure-time and occupational physical activity, alcohol consumption and smoking.ResultsThe mean BMI among the subjects was 24.7 kg/m(2), but it increased by increasing road distance (by 1.3 kg/m(2) from 5-10 to 20-184 km) and by decreasing population density (by 1.7 kg/m(2) from 1000-19,192 to 1-5 inhabitants/km(2)). The respective increases in overweight (overall prevalence 41%) were 13 per cent units for distance and 14 per cent units for population density. Adjusted regressions based on continuous explanatory variables showed an inverse L-shaped pattern with a mean BMI of 24.6 kg/m(2) at distances shorter than 5 km and a rise of 2.6 kg/m(2) at longer distances, and an increase of 2.5 kg/m(2) from highest to lowest population density. The associations with road distance were stronger for women than men, while the sex difference in association with population density remained indeterminate.ConclusionsWe conclude that young adults in Northern Finland who live far away from local centres or in the most sparsely populated areas are fatter than those who live close to local centres or in densely populated areas. The likely explanations include variations in everyday physical activity in different residential environments, although causality of the associations remains to be confirmed.

Dataset Information

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.

Publications

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.

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