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

Nicole M Warrington; Laura D Howe; Lavinia Paternoster; Marika Kaakinen; Sauli Herrala; Ville Huikari; Yan Yan Wu; John P Kemp; Nicholas J Timpson; Beate St Pourcain; George Davey Smith; Kate Tilling; Marjo-Riitta Jarvelin; Craig E Pennell; David M Evans; Debbie A Lawlor; Laurent Briollais; Lyle J Palmer

doi:10.1093/ije/dyv077

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

Int J Epidemiol. 2015 Apr;44(2):700-12. doi: 10.1093/ije/dyv077. Epub 2015 May 7.

Authors

Nicole M Warrington¹, Laura D Howe¹, Lavinia Paternoster¹, Marika Kaakinen¹, Sauli Herrala², Ville Huikari², Yan Yan Wu², John P Kemp¹, Nicholas J Timpson¹, Beate St Pourcain¹, George Davey Smith¹, Kate Tilling¹, Marjo-Riitta Jarvelin¹, Craig E Pennell², David M Evans¹, Debbie A Lawlor¹, Laurent Briollais², Lyle J Palmer²

Affiliations

¹ School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK, Biocenter Oulu, and Institute of Health Sciences, University of Oulu, Oulu, Finland, Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, UK, Unit of Primary Care, Oulu University Hospital, Oulu, Finland and The Joanna Briggs Institute, The Robinson Research Institute, and School of Translational Health Science, University of Adelaide, Adelaide, SA, Australia School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK, Biocenter Oulu, and Institute of Health Sciences, University of Oulu, Oulu, Finland, Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, UK, Unit of Prim
² School of Women's and Infants' Health, University of Western Australia, Perth, WA, Australia, University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK, School of Social and Community Medicine, University of Bristol, Bristol, UK, Biocenter Oulu, and Institute of Health Sciences, University of Oulu, Oulu, Finland, Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada, Department of Children and Young People and Families, National Institute for Health and Welfare, Oulu, Finland, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, London, UK, Unit of Primary Care, Oulu University Hospital, Oulu, Finland and The Joanna Briggs Institute, The Robinson Research Institute, and School of Translational Health Science, University of Adelaide, Adelaide, SA, Australia.

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.

Keywords: ALSPAC; Body mass index; Raine; childhood; genome-wide association study; trajectory.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adenylyl Cyclases / genetics
Adolescent
Body Height / genetics
Body Mass Index*
Body Weight / genetics
Child
Child, Preschool
Chromosomes, Human, Pair 9 / genetics
Female
Genome-Wide Association Study
Genotype
Granulocyte Colony-Stimulating Factor / genetics
Humans
Infant
Male
Mutation, Missense / genetics
Pediatric Obesity / genetics*
Polymorphism, Single Nucleotide / genetics*
RNA-Binding Proteins / genetics*
Receptor, Melanocortin, Type 4 / genetics

Substances

FAM120A protein, human
MC4R protein, human
OLFM4 protein, human
RNA-Binding Proteins
Receptor, Melanocortin, Type 4
Granulocyte Colony-Stimulating Factor
Adenylyl Cyclases
adenylate cyclase 3

Abstract

Publication types

MeSH terms

Substances

Grants and funding