DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.
DNA methylation at the suppressor of cytokine signaling 3 (SOCS3) gene influences height in childhood.
复制标题
DOI：
10.1038/s41467-023-40607-0
复制
发表时间：
2023-08-25
影响因子：
16.6
通讯作者：
Chandak, Giriraj R.
中科院分区：
文献类型：
--
作者：
Issarapu, Prachand;Arumalla, Manisha;Elliott, Hannah R.;Nongmaithem, Suraj S.;Sankareswaran, Alagu;Betts, Modupeh;Sajjadi, Sara;Kessler, Noah J.;Bayyana, Swati;Mansuri, Sohail R.;Derakhshan, Maria;Krishnaveni, G. V.;Shrestha, Smeeta;Kumaran, Kalyanaraman;Di Gravio, Chiara;Sahariah, Sirazul A.;Sanderson, Eleanor;Relton, Caroline L.;Ward, Kate A.;Moore, Sophie E.;Prentice, Andrew M.;Lillycrop, Karen A.;Fall, Caroline H. D.;Silver, Matt J.;Chandak, Giriraj R.
人类身高很大程度上受到遗传因素的影响，但可改变的表观遗传因素的作用尚未得到充分研究，特别是在低收入和中等收入国家(LMIC)。我们调查了四个LMIC队列(n = 1927)中血液DNA甲基化与儿童身高之间的联系，并在高收入国家队列(n = 879)中发现了在三个CPG中细胞因子信号转导抑制基因(SOCS3)复制的强大关联。SOCS3甲基化(SOCS3m)-身高关联不受遗传效应的影响。孟德尔随机化分析证实了SOCS3m对身高的因果影响。在纵向分析中，SOCS3m最大可解释儿童中期身高变异的9.5%，而由身高多基因风险分数解释的变异从出生到21岁逐渐增加。儿童的SOCS3m与产前母亲的叶酸和社会经济地位有关。体外鉴定证实了SOCS3m对基因表达的调节作用。我们的发现表明，表观遗传修饰可能在LMIC的儿童身高驱动中发挥重要作用。在这里，作者在印度、冈比亚和英国的儿童中发现了细胞因子信号抑制因子3(SOCS3)甲基化与身高之间的关联。
Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts (n = 1927) and identify a robust association at three CpGs in the suppressor of cytokine signaling 3 (SOCS3) gene which replicates in a high-income country cohort (n = 879). SOCS3 methylation (SOCS3m)—height associations are independent of genetic effects. Mendelian randomization analysis confirms a causal effect of SOCS3m on height. In longitudinal analysis, SOCS3m explains a maximum 9.5% of height variance in mid-childhood while the variance explained by height polygenic risk score increases from birth to 21 years. Children’s SOCS3m is associated with prenatal maternal folate and socio-economic status. In-vitro characterization confirms a regulatory effect of SOCS3m on gene expression. Our findings suggest epigenetic modifications may play an important role in driving child height in LMIC. Here the authors identify an association between methylation of the suppressor of cytokine signaling 3 (SOCS3) and height in children from India, Gambia and the UK.
登录
查看更多内容
影响因子：
3.4
作者：
Duan WN;Xia ZY;Liu M;Sun Q;Lei SQ;Wu XJ;Meng QT;Leng Y
通讯作者：
Leng Y
影响因子：
5.5
作者：
Stovitz, Steven D.;Hannan, Peter J.;Lytle, Leslie A.;Demerath, Ellen W.;Pereira, Mark A.;Himes, John H.
通讯作者：
Himes, John H.
影响因子：
7.7
作者：
Galanter, Joshua M.;Gignoux, Christopher R.;Zaitlen, Noah
通讯作者：
Zaitlen, Noah
DOI：
10.1152/ajpheart.00570.2012
发表时间：
2013-03-01
影响因子：
4.8
作者：
Dhar, Kajari;Rakesh, Kriti;Agrawal, Devendra K.
通讯作者：
Agrawal, Devendra K.
影响因子：
4.5
作者：
Hall MD;Murray CA;Valdez MJ;Perantoni AO
通讯作者：
Perantoni AO