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Felix, J.F.* ; Bradfield, J.P.* ; Monnereau, C.* ; van der Valk, R.J.* ; Stergiakouli, E.* ; Chesi, A.* ; Gaillard, R.* ; Feenstra, B.* ; Thiering, E. ; Kreiner-Møller, E.* ; Mahajan, A.* ; Pitkänen, N.* ; Joro, R.* ; Cavadino, A.* ; Huikari, V.* ; Franks, S.* ; Groen-Blokhuis, M.M.* ; Cousminer, D.L.* ; Marsh, J.A.* ; Lehtimäki, T.* ; Curtin, J.A.* ; Vioque, J.* ; Ahluwalia, T.S.* ; Myhre, R.* ; Price, T.S.* ; Vilor-Tejedor, N.* ; Yengo, L.* ; Grarup, N.* ; Ntalla, I.* ; Ang, W.* ; Atalay, M.* ; Bisgaard, H.* ; Blakemore, A.I.* ; Bonnefond, A.* ; Carstensen, L.* ; Eriksson, J.* ; Flexeder, C. ; Franke, L.* ; Geller, F.* ; Geserick, M.* ; Hartikainen, A.L.* ; Haworth, C.M.* ; Hirschhorn, J.N.* ; Hofman, A.* ; Holm, J.C.* ; Horikoshi, M.* ; Hottenga, J.J.* ; Huang, J.* ; Kadarmideen, H.N.* ; Kähönen, M.* ; Kiess, W.* ; Lakka, H.M.* ; Lakka, T.A.* ; Lewin, A.M.* ; Liang, L.* ; Lyytikäinen, L.-P.* ; Ma, B.* ; Magnus, P.* ; McCormack, S.E.* ; McMahon, G.* ; Mentch, F.D.* ; Middeldorp, C.M.* ; Murray, C.S.* ; Pahkala, K.* ; Pers, T.H.* ; Pfäffle, R.* ; Postma, D.S.* ; Power, C.* ; Simpson, A.* ; Sengpiel, V.* ; Tiesler, C.M. ; Torrent, M.* ; Uitterlinden, A.G.* ; van Meurs, J.B.* ; Vinding, R.* ; Waage, J.* ; Wardle, J.* ; Zeggini, E.* ; Zemel, B.S.* ; Dedoussis, G.V.* ; Pedersen, O.* ; Froguel, P.* ; Sunyer, J.* ; Plomin, R.* ; Jacobsson, B.* ; Hansen, T.* ; Gonzalez, J.R.* ; Custovic, A.* ; Raitakari, O.T.* ; Pennell, C.E.* ; Widen, E.* ; Boomsma, D.I.* ; Koppelman, G.H.* ; Sebert, S.* ; Jarvelin, M.R.* ; Hyppönen, E.* ; McCarthy, M.I.* ; Lindi, V.* ; Harri, N.* ; Körner, A.* ; Bønnelykke, K.* ; Heinrich, J. ; Melbye, M.* ; Rivadeneira, F.* ; Hakonarson, H.* ; Ring, S.M.* ; Smith, G.D.* ; Sørensen, T.I.* ; Timpson, N.J.* ; Grant, S.F.A.* ; Jaddoe, V.W.*

Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.

Hum. Mol. Genet. 25, 389-403 (2016)
Publ. Version/Full Text Postprint Research data DOI
Open Access Green
A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35,668 children from 20 studies in the discovery phase and 11,873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide-significance (P-value<5 x 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B, and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) (Standard Error (SE) 0.007), 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503, and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value=3.12 x 10(-10)) increase in childhood body mass index in a population of 1,955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Environmental-factors; Fat Distribution; Gene; Obesity; Metaanalysis; Expression; Weight; Adam23; Variants; Insights
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Quellenangaben Volume: 25, Issue: 2, Pages: 389-403 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Oxford
Reviewing status Peer reviewed