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跨平台方法发现人类代谢和健康的遗传调控因子
2021-01-09 21:22

英国剑桥大学Claudia Langenberg小组通过跨平台方法确定了人类代谢和健康的遗传调控因子。该项研究成果发表在2021年1月7日出版的《自然—遗传学》杂志上。

在对174种代谢物的跨平台分析中,研究人员确定了499个关联(P <4.9×10-10),其特征是多效性、等位基因异质性、大且非线性效应以及非同义变异的富集。研究人员确定在瓜氨酸水平、体重指数、空腹葡萄糖依赖的促胰岛素肽和2型糖尿病之间共享的GLP2R(p.Asp470Asn)信号,并以β-arrestin信号作为潜在机制。

遗传上更高的丝氨酸水平显示出能够降低可能性(降低95%)并预测2型黄斑毛细血管扩张的进展,这是一种罕见的变性视网膜疾病。跨平台基因组数据和小分子数据的集成使人们能够发现人类代谢调节因子,并将其转化为临床使用。

附:英文原文

Title: A cross-platform approach identifies genetic regulators of human metabolism and health

Author: Luca A. Lotta, Maik Pietzner, Isobel D. Stewart, Laura B. L. Wittemans, Chen Li, Roberto Bonelli, Johannes Raffler, Emma K. Biggs, Clare Oliver-Williams, Victoria P. W. Auyeung, Jianan Luan, Eleanor Wheeler, Ellie Paige, Praveen Surendran, Gregory A. Michelotti, Robert A. Scott, Stephen Burgess, Verena Zuber, Eleanor Sanderson, Albert Koulman, Fumiaki Imamura, Nita G. Forouhi, Kay-Tee Khaw, Julian L. Griffin, Angela M. Wood, Gabi Kastenmller, John Danesh, Adam S. Butterworth, Fiona M. Gribble, Frank Reimann, Melanie Bahlo, Eric Fauman, Nicholas J. Wareham, Claudia Langenberg

Issue&Volume: 2021-01-07

Abstract: In cross-platform analyses of 174 metabolites, we identify 499 associations (P<4.9×1010) characterized by pleiotropy, allelic heterogeneity, large and nonlinear effects and enrichment for nonsynonymous variation. We identify a signal at GLP2R (p.Asp470Asn) shared among higher citrulline levels, body mass index, fasting glucose-dependent insulinotropic peptide and type 2 diabetes, with β-arrestin signaling as the underlying mechanism. Genetically higher serine levels are shown to reduce the likelihood (by 95%) and predict development of macular telangiectasia type 2, a rare degenerative retinal disease. Integration of genomic and small molecule data across platforms enables the discovery of regulators of human metabolism and translation into clinical insights.

DOI: 10.1038/s41588-020-00751-5

Source: https://www.nature.com/articles/s41588-020-00751-5

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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