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Get Free AccessA 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.
Adnan Ćustović, Olli T. Raitakari, Craig E. Pennell, Elisabeth Widén, Dorret I. Boomsma, Gerard H. Koppelman, Sylvain Sebért, Paul M Ridker, Elina Hyppönen, Mark I. McCarthy, Virpi Lindi, Harri Niinikoski, Antje Körner, 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 Pitkänen, Raimo Joro, Alana Cavadino, Ville Huikari, Steve Franks, Maria M. Groen‐Blokhuis, Diana L. Cousminer, Julie Marsh, Terho Lehtimäki, John A. Curtin, Jesús Vioqué, Tarunveer S. Ahluwalia, Ronny Myhre, Thomas S. Price, Natàlia Vilor‐Tejedor, Loïc Yengo, Niels Grarup, Ιωάννα Ντάλλα, Wei Ang, Mustafa Atalay, Hans Bisgaard, Alexandra I. F. Blakemore, Amélie Bonnefond, Lisbeth Carstensen, Johan G. 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, Alex Lewin, Liming Liang, Leo‐Pekka Lyytikäinen, Baoshan Ma, Per Magnus, Shana E. McCormack, George McMahon, Frank Mentch, Christel M. Middeldorp, Clare Murray, Katja Pahkala, Tune H. Pers, Roland Pfäffle, Dirkje S. Postma, Christopher Power, Angela Simpson, Verena Sengpiel, Carla M. T. Tiesler, Maties Torrent, André G. Uitterlinden, Joyce B. J. van Meurs, Rebecca Vinding, Johannes Waage, Jane Wardle, Eleftheria Zeggini, Babette S. Zemel, George Dedoussis, Oluf Pedersen, Philippe Froguel, Jordi Sunyer, Robert Plomin, Bo Jacobsson, Torben Hansen, Juan R. González (2015). Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. , 25(2), DOI: https://doi.org/10.1093/hmg/ddv472.
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Type
Article
Year
2015
Authors
100
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1093/hmg/ddv472
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