A genome-wide perspective of genetic variation in human metabolism.
A genome-wide perspective of genetic variation in human metabolism.
复制标题
作者：
血清代谢物浓度提供了人体生物过程的直接读数，并与心血管和代谢性疾病等疾病有关。在这里，我们提出了一项涉及163个代谢性状的全基因组关联研究，研究对象是来自KORA人群的1809名参与者，在TwinsUK队列中随访了422名参与者。在9个复制位点中的8个（FADS1, ELOVL2， ACADS， ACADM， ACADL, SPTLC3， ETFDH, SLC16A9）中，遗传变异位于酶或溶质载体编码基因中或附近，相关代谢性状与蛋白质的功能相匹配。许多这样的基因座位于重要酶促反应的限速步骤中。使用代谢物浓度比率作为酶促反应速率的代谢物浓度比率可以减少方差，并产生与3×10−24和6.5×10−179之间的p值之间的强大统计关联。这些基因座解释了5.6%至36.3%的观察方差。对于一些基因座，与临床相关参数的关联先前已被报道。
Serum metabolite concentrations provide a direct readout of biological processes in the human body, and are associated with disorders such as cardiovascular and metabolic diseases. Here we present a genome-wide association study with 163 metabolic traits using 1809 participants from the KORA population, followed up in the TwinsUK cohort with 422 participants. In eight out of nine replicated loci (FADS1, ELOVL2, ACADS, ACADM, ACADL, SPTLC3, ETFDH, SLC16A9) the genetic variant is located in or near enzyme or solute carrier coding genes, where the associating metabolic traits match the proteins’ function. Many of these loci are located in rate limiting steps of important enzymatic reactions. Use of metabolite concentration ratios as proxies for enzymatic reaction rates reduces the variance and yields robust statistical associations with p-values between 3×10−24 and 6.5×10−179. These loci explained 5.6% to 36.3% of the observed variance. For several loci, associations with clinically relevant parameters have previously been reported.
登录
查看更多内容
影响因子：
3.7
作者：
Wang-Sattler, Rui;Yu, Yao;Mittelstrass, Kirstin;Lattka, Eva;Altmaier, Elisabeth;Gieger, Christian;Ladwig, Karl H.;Dahmen, Norbert;Weinberger, Klaus M.;Hao, Pei;Liu, Lei;Li, Yixue;Wichmann, H. -Erich;Adamski, Jerzy;Suhre, Karsten;Illig, Thomas
通讯作者：
Illig, Thomas
与人类血液低密度脂蛋白胆固醇、高密度脂蛋白胆固醇或甘油三酯相关的六个新位点。
影响因子：
30.8
作者：
Kathiresan, Sekar;Melander, Olle;Guiducci, Candace;Surti, Aarti;Burtt, Noel P.;Rieder, Mark J.;Cooper, Gregory M.;Roos, Charlotta;Voight, Benjamin F.;Havulinna, Aki S.;Wahlstrand, Bjorn;Hedner, Thomas;Corella, Dolores;Tai, E. Shyong;Ordovas, Jose M.;Berglund, Goran;Vartiainen, Erkki;Jousilahti, Pekka;Hedblad, Bo;Taskinen, Marja-Riitta;Newton-Cheh, Christopher;Salomaa, Veikko;Peltonen, Leena;Groop, Leif;Altshuler, David M.;Orho-Melander, Marju
通讯作者：
Orho-Melander, Marju
影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
影响因子：
3.7
作者：
Gross E;Busse B;Riemenschneider M;Neubauer S;Seck K;Klein HG;Kiechle M;Lordick F;Meindl A
通讯作者：
Meindl A
影响因子：
3.8
作者：
Nagan, N;Kruckeberg, KE;Matern, D
通讯作者：
Matern, D