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)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Environmental-factors; Fat Distribution; Gene; Obesity; Metaanalysis; Expression; Weight; Adam23; Variants; Insights
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2016
Prepublished im Jahr
2015
HGF-Berichtsjahr
2015
ISSN (print) / ISBN
0964-6906
e-ISSN
1460-2083
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 25,
Heft: 2,
Seiten: 389-403
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Oxford University Press
Verlagsort
Oxford
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
POF Topic(s)
30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er)
Genetics and Epidemiology
PSP-Element(e)
G-503900-001
G-503900-003
Förderungen
Copyright
Erfassungsdatum
2015-12-07