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

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Janine F. Felix, Jonathan P. Bradfield, Claire Monnereau, Ralf J.p. Van Der Valk, Evie Stergiakouli, Alessandra Chesi, Romy Gaillard, Bjarke Feenstra, Elisabeth Thiering, Eskil Kreiner-Møller, Anubha Mahajan, Niina Pitk??nen, Raimo Joro, Alana Cavadino, Ville Huikari, Steve Franks, Maria M. Groen-blokhuis, Diana L. Cousminer, Julie A. Marsh, Terho Lehtimäki & 91 more John A. Curtin, Jesus Vioque, Tarunveer S. Ahluwalia, Ronny Myhre, Thomas S. Price, Natalia Vilor-tejedor, Loïc Yengo, Niels Grarup, Ioanna Ntalla, Wei Ang, Mustafa Atalay, Hans Bisgaard, Alexandra I. Blakemore, Amelie Bonnefond, Lisbeth Carstensen, Johan Eriksson, Claudia Flexeder, Lude Franke, Frank Geller, Mandy Geserick, Anna-liisa Hartikainen, Claire M.a. Haworth, Joel N. Hirschhorn, Albert Hofman, Jens-christian Holm, Momoko Horikoshi, Jouke Jan Hottenga, Jinyan Huang, Haja N. Kadarmideen, Mika Kähönen, Wieland Kiess, Hanna-maaria Lakka, Timo A. Lakka, Alexandra M. Lewin, Liming Liang, Leo-pekka Lyytikäinen, Baoshan Ma, Per Magnus, Shana E. Mccormack, George Mcmahon, Frank D. Mentch, Christel M. Middeldorp, Clare S. Murray, Katja Pahkala, Tune H. Pers, Roland Pfäffle, Dirkje S. Postma, Christine Power, Angela Simpson, Verena Sengpiel, Carla M. T. Tiesler, Maties Torrent, André G. Uitterlinden, Joyce B. Van Meurs, Rebecca Vinding, Johannes Waage, Jane Wardle, Eleftheria Zeggini, Babette S. Zemel, George V. Dedoussis, Oluf Pedersen, Philippe Froguel, Jordi Sunyer, Robert Plomin, Bo Jacobsson, Torben Hansen, Juan R. Gonzalez, Adnan Custovic, Olli T. Raitakari, Craig E. Pennell, Elisabeth Widøn, Dorret I. Boomsma, Gerard H. Koppelman, Sylvain Sebert, Marjo-riitta Jørvelin, Elina Hyppønen, Mark I. Mccarthy, Virpi Lindi, Niinikoski Harri, Antje Kørner, Klaus Bønnelykke, Joachim Heinrich, Mads Melbye, Fernando Rivadeneira, Hakon Hakonarson, Susan M. Ring, George Davey Smith, Thorkild I.a. Sørensen, Nicholas J. Timpson, Struan F.a. Grant, Vincent W.v. Jaddoe

Original languageEnglish
Pages (from-to)389-403
JournalHuman Molecular Genetics
Volume25
Early online date24 Nov 2015
DOIs
Publication statusE-pub ahead of print - 24 Nov 2015

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Abstract

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 × 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 × 10−10) increase in childhood body mass index in a population of 1955 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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