Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
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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. |
| Year of Publication | 2016
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| Journal | Hum Mol Genet
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| Volume | 25
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| Issue | 2
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| Pages | 389-403
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| Date Published | 2016 Jan 15
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| ISSN | 1460-2083
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| URL | |
| DOI | 10.1093/hmg/ddv472
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| PubMed ID | 26604143
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| PubMed Central ID | PMC4854022
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| Grant list | U01HG004446 / HG / NHGRI NIH HHS / United States
R01 CA166945 / CA / NCI NIH HHS / United States
MC_UU_12013/1-9 / Medical Research Council / United Kingdom
R01 MH063706 / MH / NIMH NIH HHS / United States
U01HG004438 / HG / NHGRI NIH HHS / United States
MOP-82893 / Canadian Institutes of Health Research / Canada
U01 HG004438 / HG / NHGRI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
R01 HL087679 / HL / NHLBI NIH HHS / United States
MC_UU_12013/3 / Medical Research Council / United Kingdom
14133 / Cancer Research UK / United Kingdom
R01 HD58886 / HD / NICHD NIH HHS / United States
5R01MH63706:02 / MH / NIMH NIH HHS / United States
Biotechnology and Biological Sciences Research Council / United Kingdom
MR/K002449/1 / Medical Research Council / United Kingdom
1RL1MH083268-01 / MH / NIMH NIH HHS / United States
U01 NS047537 / NS / NINDS NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
G0601361 / Medical Research Council / United Kingdom
102215 / Wellcome Trust / United Kingdom
N01ES75558 / ES / NIEHS NIH HHS / United States
076113 / Wellcome Trust / United Kingdom
R01 HD076321 / HD / NICHD NIH HHS / United States
MR/N01104X/1 / Medical Research Council / United Kingdom
U01 DK062418 / DK / NIDDK NIH HHS / United States
K23 DK102659 / DK / NIDDK NIH HHS / United States
MC_PC_15018 / Medical Research Council / United Kingdom
R01 HD056465 / HD / NICHD NIH HHS / United States
P30 ES013508 / ES / NIEHS NIH HHS / United States
102215/2/13/2 / Wellcome Trust / United Kingdom
G19/2 / Medical Research Council / United Kingdom
G0802782 / Medical Research Council / United Kingdom
U01HG004423 / HG / NHGRI NIH HHS / United States
090367 / Wellcome Trust / United Kingdom
085475/B/08/Z / Wellcome Trust / United Kingdom
2 UO1 NS 047537-06A1 / NS / NINDS NIH HHS / United States
R01 HD058886 / HD / NICHD NIH HHS / United States
G0500079 / Medical Research Council / United Kingdom
UL1 TR001425 / TR / NCATS NIH HHS / United States
G0901245 / Medical Research Council / United Kingdom
UL1 TR000077 / TR / NCATS NIH HHS / United States
068545/Z/02 / Wellcome Trust / United Kingdom
5R01HL087679-02 / HL / NHLBI NIH HHS / United States
RL1 MH083268 / MH / NIMH NIH HHS / United States
U01 HG004423 / HG / NHGRI NIH HHS / United States
098381 / Wellcome Trust / United Kingdom
1 UO1 NS 047537-01 / NS / NINDS NIH HHS / United States
G0000934 / Medical Research Council / United Kingdom
085475/Z/08/Z / Wellcome Trust / United Kingdom
MR/M012638/1 / Medical Research Council / United Kingdom
G9815508 / Medical Research Council / United Kingdom
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