Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index
Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index
复制标题
全基因组关联分析确定了儿童体重指数的三个新的易感位点。
DOI：
10.1093/hmg/ddv472
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发表时间：
2016-01-15
影响因子：
3.5
通讯作者：
Jaddoe, Vincent W. V.
中科院分区：
文献类型：
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作者：
Felix, Janine F.;Bradfield, Jonathan P.;Jaddoe, Vincent W. V.
大量的遗传位点与成人体重指数相关。然而，儿童体重指数的遗传学在很大程度上是未知的。我们使用性别和年龄调整的标准差分数对儿童体重指数的全基因组关联研究进行了荟萃分析。我们纳入了来自20项发现阶段研究的35668名儿童和来自13项重复阶段研究的11873名儿童。在联合发现和复制分析中，总共有15个基因座达到全基因组显著性（P值< 5 x 10（-8）），其中12个是先前鉴定的与成人体重指数或儿童肥胖相关的ADCY 3、GNPDA 2、TMEM 18、SEC 16 B、FAIM 2、FTO、TFAP 2B、TNNI 3 K、MC 4 R、GPR 61、LMX 1B和OLFM 4中或附近的基因座。我们发现了三个新的基因座：位于ELP 3附近的rs 13253111，位于RAB 27 B附近的rs 8092503和位于ADAM 23附近的rs 13387838。每增加一个风险等位基因，rs 13253111、rs 8092503和rs 13387838的体重指数分别增加0.04标准差评分（SDS）[标准误（SE）0.007]、0.05 SDS（SE 0.008）和0.14 SDS（SE 0.025）。结合所有15个SNPs的遗传风险评分显示，在1955名儿童的人群中，每增加一个平均风险等位基因与儿童期体重指数增加0.073 SDS（SE 0.011，P值= 3.12 x 10（-10））相关。该风险评分解释了儿童体重指数2%的变异。这项研究强调了儿童和成人体重指数之间共有的遗传背景，并增加了三个新的基因座。这些位点可能代表了与体重指数相关性强度的年龄相关差异。
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 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 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.