A genome-wide association study of serum proteins reveals shared loci with common diseases.
A genome-wide association study of serum proteins reveals shared loci with common diseases.
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DOI：
10.1038/s41467-021-27850-z
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发表时间：
2022-01-25
影响因子：
16.6
通讯作者：
Gudnason V
中科院分区：
文献类型：
--
作者：
Gudjonsson A;Gudmundsdottir V;Axelsson GT;Gudmundsson EF;Jonsson BG;Launer LJ;Lamb JR;Jennings LL;Aspelund T;Emilsson V;Gudnason V
随着遗传关联研究的不断增多，基因型-表型图谱变得越来越复杂，但大多数疾病相关等位基因的功能后果尚不清楚。测量固体组织和生物体液中与遗传变异相结合的蛋白质水平变化，为深入了解功能提供了一条途径。在此，我们对 5,368 名个体进行了大规模蛋白质组学研究，揭示了遗传变异与 2,091 种血清蛋白之间的 4,035 个独立关联，其中 36% 之前未报告。大多数顺式和反式作用遗传信号对于单个蛋白质来说都是独特的，尽管我们的结果还强调了对蛋白质水平的许多高度多效性遗传效应，并证明蛋白质的遗传关联谱反映了蛋白质的某些特征，包括其在蛋白质网络中的位置、组织特异性和对功能缺失突变的不耐受性。将蛋白质测量与队列的深层表型分析相结合，我们观察到受已建立的 GWAS 位点调节的血清蛋白表型关联性的显着富集，并为遗传学、血清蛋白水平和复杂疾病之间的相互作用提供了新的见解。循环蛋白与许多疾病有关，了解它们的遗传控制可以帮助我们了解疾病。在这里，作者将常见的遗传变异与蛋白质水平联系起来，发现遗传关联与循环蛋白质和复杂疾病的重叠。
With the growing number of genetic association studies, the genotype-phenotype atlas has become increasingly more complex, yet the functional consequences of most disease associated alleles is not understood. The measurement of protein level variation in solid tissues and biofluids integrated with genetic variants offers a path to deeper functional insights. Here we present a large-scale proteogenomic study in 5,368 individuals, revealing 4,035 independent associations between genetic variants and 2,091 serum proteins, of which 36% are previously unreported. The majority of both cis- and trans-acting genetic signals are unique for a single protein, although our results also highlight numerous highly pleiotropic genetic effects on protein levels and demonstrate that a protein’s genetic association profile reflects certain characteristics of the protein, including its location in protein networks, tissue specificity and intolerance to loss of function mutations. Integrating protein measurements with deep phenotyping of the cohort, we observe substantial enrichment of phenotype associations for serum proteins regulated by established GWAS loci, and offer new insights into the interplay between genetics, serum protein levels and complex disease. Circulating proteins have been linked to many conditions, and understanding their genetic control can lead to understanding of disease. Here, the authors associate common genetic variants with protein levels, finding overlap of genetic associations with circulating proteins and complex disease.
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影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ