人类代谢中遗传变异的全基因组视角。
A genome-wide perspective of genetic variation in human metabolism.
机构信息
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
出版信息
Nat Genet. 2010 Feb;42(2):137-41. doi: 10.1038/ng.507. Epub 2009 Dec 27.
Abstract
Serum metabolite concentrations provide a direct readout of biological processes in the human body, and they are associated with disorders such as cardiovascular and metabolic diseases. We present a genome-wide association study (GWAS) of 163 metabolic traits measured in human blood from 1,809 participants from the KORA population, with replication in 422 participants of the TwinsUK cohort. For eight out of nine replicated loci (FADS1, ELOVL2, ACADS, ACADM, ACADL, SPTLC3, ETFDH and SLC16A9), the genetic variant is located in or near genes encoding enzymes or solute carriers whose functions match the associating metabolic traits. In our study, the use of metabolite concentration ratios as proxies for enzymatic reaction rates reduced the variance and yielded robust statistical associations with P values ranging from 3 x 10(-24) to 6.5 x 10(-179). These loci explained 5.6%-36.3% of the observed variance in metabolite concentrations. For several loci, associations with clinically relevant parameters have been reported previously.
摘要
血清代谢物浓度提供了人体生物过程的直接读数，并且与心血管和代谢疾病等疾病有关。我们对来自 KORA 人群的 1809 名参与者的血液中测量的 163 种代谢特征进行了全基因组关联研究（GWAS），并在来自 TwinsUK 队列的 422 名参与者中进行了复制。对于九个复制的基因座中的八个（FADS1、ELOVL2、ACADS、ACADM、ACADL、SPTLC3、ETFDH 和 SLC16A9），遗传变异位于或靠近编码酶或溶质载体的基因内或附近，其功能与关联的代谢特征相匹配。在我们的研究中，使用代谢物浓度比作为酶促反应速率的替代物，减少了方差，并产生了与 P 值范围为 3 x 10(-24) 至 6.5 x 10(-179) 的稳健统计关联。这些基因座解释了代谢物浓度观察到的方差的 5.6%-36.3%。对于一些基因座，先前已经报道了与临床相关参数的关联。
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