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Nature:英国科学家揭示出生体重与成年疾病的遗传关联关系

摘要 : 2016年9月29日,国际学术权威刊物自然出版集团旗下子刊《Nature》杂志在线发表了英国牛津大学科学家Mark I. McCarthy和埃克塞特大学医学院Rachel M. Freathy研究员的一篇研究论文

 2016年9月29日,国际学术权威刊物自然出版集团旗下子刊《Nature》杂志在线发表了英国牛津大学科学家Mark I. McCarthy和埃克塞特大学医学院Rachel M. Freathy研究员的一篇研究论文,研究指出在出生体重和成年时疾病易感性(如Ⅱ型糖尿病和心血管疾病)之间的关系中,遗传因素起到了重要的作用。这项研究分析了与出生体重相关的60个基因组区域,其中大多数都从未被识别出来。

出生体重是指婴儿诞下后不久第一次称重的重量,通常在出生一个小时里进行测量。出生体重不但与新生儿死亡率和发病率相关,还会对成年后的健康带来一定影响,譬如出生体重异常一直被看作是成年期糖代谢异常的独立危险因素,也与成年期心血管疾病(如高血压)有关联。尽管先前的研究曾报告过出生体重和未来疾病风险之间的联系,但遗传变异在这一关系中发挥的作用,长期以来并不明确。

研究人员结合了37个研究中对出生体重的全基因组关联分析(GWAS)数据进行考察,涉及153781位拥有不同祖先的个体,包括欧洲人、非裔美国人、中国人、菲律宾人、苏里南人和摩洛哥人。首先,他们识别了胎儿基因型与出生体重有关的60个基因组区域。随后,他们研究了这些遗传关联,以理解出生体重与疾病之间的关系。研究人员发现,出生体重与成年时患上Ⅱ型糖尿病和冠状动脉疾病的风险因素存在着遗传负相关性,即出生体重越是异常,成年后患上述疾病的风险越高。

研究人员提醒到,这一结果与子宫中发生的不良事件(比如营养缺乏)会在人生后期引发疾病的观点是相对的,但并不一定无法兼容。论文作者指出,未来的研究将会阐明早期事件与数十年后罹患心脏代谢疾病倾向之间的关系。

原文链接:

Genome-wide associations for birth weight and correlations with adult disease

原文摘要:

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci wher fetal genotype was associated with BW (P < 5 × 10−8). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = −0.22, P = 5.5 × 10−13), T2D (Rg = −0.27, P = 1.1 × 10−6) and coronary artery disease (Rg = −0.30, P = 6.5 × 10−9). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10−4). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

来源: Nature 浏览次数:0

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