A genome-wide association study of body mass index across early life and childhood

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Title: A genome-wide association study of body mass index across early life and childhood
Author(s): Warrington, NM
Howe, LD
Paternoster, L
Kaakinen, M
Herrala, S
Huikari, V
Wu, YY
Kemp, JP
Timpson, NJ
St Pourcain, B
Smith, GD
Tilling, K
Jarvelin, M-R
Pennell, CE
Evans, DM
Lawlor, DA
Briollais, L
Palmer, LJ
Item Type: Journal Article
Abstract: Background: Several studies have investigated the effect of known adult body mass index (BMI) associated single nucleotide polymorphisms (SNPs) on BMI in childhood. There has been no genome-wide association study (GWAS) of BMI trajectories over childhood. Methods: We conducted a GWAS meta-analysis of BMI trajectories from 1 to 17 years of age in 9377 children (77 967 measurements) from the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Western Australian Pregnancy Cohort (Raine) Study. Genome-wide significant loci were examined in a further 3918 individuals (48 530 measurements) from Northern Finland. Linear mixed effects models with smoothing splines were used in each cohort for longitudinal modelling of BMI. Results: A novel SNP, downstream from the FAM120AOS gene on chromosome 9, was detected in the meta-analysis of ALSPAC and Raine. This association was driven by a difference in BMI at 8 years (T allele of rs944990 increased BMI; PSNP = 1.52 × 10−8), with a modest association with change in BMI over time (PWald(Change) = 0.006). Three known adult BMI-associated loci (FTO, MC4R and ADCY3) and one childhood obesity locus (OLFM4) reached genome-wide significance (PWald < 1.13 × 10−8) with BMI at 8 years and/or change over time. Conclusions: This GWAS of BMI trajectories over childhood identified a novel locus that warrants further investigation. We also observed genome-wide significance with previously established obesity loci, making the novel observation that these loci affected both the level and the rate of change in BMI. We have demonstrated that the use of repeated measures data can increase power to allow detection of genetic loci with smaller sample sizes.
Publication Date: 7-May-2015
Date of Acceptance: 16-Apr-2015
URI: http://hdl.handle.net/10044/1/48221
DOI: https://dx.doi.org/10.1093/ije/dyv077
ISSN: 0300-5771
Publisher: Oxford University Press (OUP): Policy B - Oxford Open Option D
Start Page: 700
End Page: 712
Journal / Book Title: International Journal of Epidemiology
Volume: 44
Issue: 2
Copyright Statement: © 2015 The Author ; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Science & Technology
Life Sciences & Biomedicine
Public, Environmental & Occupational Health
Body mass index
genome-wide association study
trajectory
childhood
ALSPAC
Raine
ADULT OBESITY
COMMON VARIANTS
EARLY-ONSET
LOCI
GENE
BMI
WEIGHT
INFANT
FTO
DIFFERENTIATION
ALSPAC
Body mass index
Raine
childhood
genome-wide association study
trajectory
Adenylyl Cyclases
Adolescent
Body Height
Body Mass Index
Body Weight
Child
Child, Preschool
Chromosomes, Human, Pair 9
Female
Genome-Wide Association Study
Genotype
Granulocyte Colony-Stimulating Factor
Humans
Infant
Male
Mutation, Missense
Pediatric Obesity
Polymorphism, Single Nucleotide
RNA-Binding Proteins
Receptor, Melanocortin, Type 4
Chromosomes, Human, Pair 9
Humans
Body Weight
RNA-Binding Proteins
Granulocyte Colony-Stimulating Factor
Receptor, Melanocortin, Type 4
Body Mass Index
Body Height
Genotype
Mutation, Missense
Polymorphism, Single Nucleotide
Adolescent
Child
Child, Preschool
Infant
Female
Male
Genome-Wide Association Study
Pediatric Obesity
Adenylyl Cyclases
Epidemiology
0104 Statistics
1117 Public Health And Health Services
Publication Status: Published
Appears in Collections:Department of Medicine
Faculty of Medicine
Epidemiology, Public Health and Primary Care



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