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

Authors:
Dr Anubha Mahajan, PhD
Dr Anubha Mahajan, PhD
Wellcome Trust Centre for Human Genetics, University of Oxford
UK
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 Niina Pitkänen Raimo Joro Alana Cavadino Ville Huikari Steve Franks Maria M Groen-Blokhuis Diana L Cousminer Julie A Marsh Terho Lehtimäki 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 Widén Dorret I Boomsma Gerard H Koppelman Sylvain Sebert Marjo-Riitta Järvelin Elina Hyppönen Mark I McCarthy Virpi Lindi Niinikoski Harri Antje Körner 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

Hum Mol Genet 2016 Jan 24;25(2):389-403. Epub 2015 Nov 24.

The Generation R Study Group, Department of Pediatrics, Department of Epidemiology.

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.

Download full-text PDF

Source
http://hmg.oxfordjournals.org/content/early/2015/12/16/hmg.d
Web Search
http://www.hmg.oxfordjournals.org/lookup/doi/10.1093/hmg/ddv
Publisher Site
http://dx.doi.org/10.1093/hmg/ddv472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854022PMC
January 2016
228 Reads
36 Citations
6.393 Impact Factor

Publication Analysis

Top Keywords

body mass
40
childhood body
20
adult body
12
body
10
mass
10
associated adult
8
standard deviation
8
three novel
8
novel loci
8
risk allele
8
children studies
8
risk score
8
genome-wide association
8
childhood
7
loci
7
increased 004
4
deviation score
4
004 standard
4
mass increased
4
strength associations
4

References

(Supplied by CrossRef)

Similar Publications