title: Variants close to NTRK2 gene are associated with birth weight in female twins.
abstract: Low weight at birth has previously been shown to be associated with a number of adult diseases such as type 2 diabetes, cardiovascular disease, high blood pressure, and obesity later in life. Genome-wide association studies (GWAS) have been published for singleton-born individuals, but the role of genetic variation in birth weight (BW) in twins has not yet been fully investigated. A GWAS was performed in 4,593 female study participants with BW data available from the TwinsUK cohort. A genome-wide significant signal was found in chromosome 9, close to the NTRK2 gene (OMIM: 600456). QIMR, an Australian twin cohort (n = 3,003), and UK-based singleton-birth individuals from the Hertfordshire cohort (n = 2,997) were used as replication for the top two single nucleotide polymorphism (SNPs) underpinning this signal, rs12340987 and rs7849941. The top SNP, rs12340987, was found to be in the same direction in the Australian twins and in the singleton-born females (fixed effects meta-analysis beta = -0.13, SE = 0.02, and p = 1.48 × 10-8) but not in the singleton-born males tested. These findings provide an important insight into the genetic component of BW in twins who are normally excluded due to their lower BW when compared with singleton births, as well as the difference in BW between twins. The NTRK2 gene identified in this study has previously been associated with obesity.
authors.affiliation: Department of Twin Research and Genetic Epidemiology,King's College London,St Thomas' Hospital,London,UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Metrustry
authors.affiliation: MRC Lifecourse Epidemiology Unit,University of Southampton,Southampton General Hospital,Southampton,UK.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Edwards
authors.affiliation: Department of Quantitative Genetics,QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Medland
authors.affiliation: Department of Human Development and Health,Faculty of Medicine,University of Southampton,Southampton,UK.
authors.forename: John W
authors.initials: JW
authors.lastname: Holloway
authors.affiliation: Department of Molecular Epidemiology,QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.affiliation: Department of Genetic Epidemiology,QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.affiliation: Department of Twin Research and Genetic Epidemiology,King's College London,St Thomas' Hospital,London,UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: MRC Lifecourse Epidemiology Unit,University of Southampton,Southampton General Hospital,Southampton,UK.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Cooper
authors.affiliation: Department of Twin Research and Genetic Epidemiology,King's College London,St Thomas' Hospital,London,UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
mesh_terms: D001724:Birth Weight / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007231:Infant, Newborn; D020641:Polymorphism, Single Nucleotide; D020813:Receptor, trkB / Q000235:genetics*; D014427:Twins / Q000235:genetics*; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics; D006113:United Kingdom
chemical_list: D020813:Receptor, trkB