| Literature DB >> 26604143 |
Janine F Felix1, Jonathan P Bradfield2, Claire Monnereau3, Ralf J P van der Valk4, Evie Stergiakouli5, Alessandra Chesi6, Romy Gaillard3, Bjarke Feenstra7, Elisabeth Thiering8, Eskil Kreiner-Møller9, Anubha Mahajan10, Niina Pitkänen11, Raimo Joro12, Alana Cavadino13, Ville Huikari14, Steve Franks15, Maria M Groen-Blokhuis16, Diana L Cousminer17, Julie A Marsh18, Terho Lehtimäki19, John A Curtin20, Jesus Vioque21, Tarunveer S Ahluwalia22, Ronny Myhre23, Thomas S Price24, Natalia Vilor-Tejedor25, Loïc Yengo26, Niels Grarup27, Ioanna Ntalla28, Wei Ang18, Mustafa Atalay12, Hans Bisgaard9, Alexandra I Blakemore29, Amelie Bonnefond26, Lisbeth Carstensen7, Johan Eriksson30, Claudia Flexeder31, Lude Franke32, Frank Geller7, Mandy Geserick33, Anna-Liisa Hartikainen34, Claire M A Haworth35, Joel N Hirschhorn36, Albert Hofman37, Jens-Christian Holm38, Momoko Horikoshi39, Jouke Jan Hottenga16, Jinyan Huang40, Haja N Kadarmideen41, Mika Kähönen42, Wieland Kiess43, Hanna-Maaria Lakka12, Timo A Lakka44, Alexandra M Lewin45, Liming Liang46, Leo-Pekka Lyytikäinen19, Baoshan Ma47, Per Magnus48, Shana E McCormack49, George McMahon5, Frank D Mentch2, Christel M Middeldorp16, Clare S Murray20, Katja Pahkala50, Tune H Pers51, Roland Pfäffle52, Dirkje S Postma4, Christine Power53, Angela Simpson54, Verena Sengpiel55, Carla M T Tiesler8, Maties Torrent56, André G Uitterlinden57, Joyce B van Meurs58, Rebecca Vinding59, Johannes Waage9, Jane Wardle60, Eleftheria Zeggini61, Babette S Zemel62, George V Dedoussis63, Oluf Pedersen27, Philippe Froguel64, Jordi Sunyer65, Robert Plomin66, Bo Jacobsson67, Torben Hansen27, Juan R Gonzalez25, Adnan Custovic20, Olli T Raitakari68, Craig E Pennell18, Elisabeth Widén17, Dorret I Boomsma16, Gerard H Koppelman69, Sylvain Sebert70, Marjo-Riitta Järvelin71, Elina Hyppönen72, Mark I McCarthy73, Virpi Lindi12, Niinikoski Harri74, Antje Körner43, Klaus Bønnelykke9, Joachim Heinrich31, Mads Melbye75, Fernando Rivadeneira57, Hakon Hakonarson76, Susan M Ring77, George Davey Smith5, Thorkild I A Sørensen78, Nicholas J Timpson5, Struan F A Grant79, Vincent W V Jaddoe3.
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.Entities:
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Year: 2015 PMID： 26604143 PMCID： PMC4854022 DOI： 10.1093/hmg/ddv472
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150