Coding and regulatory variants are associated with serum protein levels and disease.
Coding and regulatory variants are associated with serum protein levels and disease.
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DOI：
10.1038/s41467-022-28081-6
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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：
Emilsson V;Gudmundsdottir V;Gudjonsson A;Jonmundsson T;Jonsson BG;Karim MA;Ilkov M;Staley JR;Gudmundsson EF;Launer LJ;Lindeman JH;Morton NM;Aspelund T;Lamb JR;Jennings LL;Gudnason V
循环蛋白可用于诊断和预测疾病相关的结果。一项深入的血清蛋白质组研究最近揭示了血清蛋白质网络与常见疾病之间的密切联系。在目前的研究中，将54，469个低频和常见的外显子组阵列变体与来自AGES雷克雅未克队列的5343名个体血清中的4782个蛋白质测量值进行了比较。该分析鉴定了大量具有与许多疾病的遗传特征重叠的遗传特征的血清蛋白。更具体地说，使用研究范围内的显著性阈值，我们发现2021个独立的外显子组阵列变体与1942种蛋白质的血清水平相关。这些变异存在于数百种复杂疾病特征所共有的遗传基因座中，突出了血清蛋白作为生物标志物和多种疾病的潜在致病因子的新兴作用。找到蛋白质表达的遗传基础可以阐明疾病的遗传机制。在这里，作者将低频率和常见的DNA序列变异与数千种血清蛋白联系起来，发现循环蛋白与广泛的常见疾病之间存在遗传重叠。
Circulating proteins can be used to diagnose and predict disease-related outcomes. A deep serum proteome survey recently revealed close associations between serum protein networks and common disease. In the current study, 54,469 low-frequency and common exome-array variants were compared to 4782 protein measurements in the serum of 5343 individuals from the AGES Reykjavik cohort. This analysis identifies a large number of serum proteins with genetic signatures overlapping those of many diseases. More specifically, using a study-wide significance threshold, we find that 2021 independent exome array variants are associated with serum levels of 1942 proteins. These variants reside in genetic loci shared by hundreds of complex disease traits, highlighting serum proteins’ emerging role as biomarkers and potential causative agents of a wide range of diseases. Finding the genetic basis of protein expression can elucidate the genetic mechanisms of disease. Here, the authors link low-frequency and common DNA sequence variants to thousands of serum proteins, finding genetic overlap between circulating proteins and a wide range of common diseases.
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影响因子：
4.6
作者：
Candia J;Cheung F;Kotliarov Y;Fantoni G;Sellers B;Griesman T;Huang J;Stuccio S;Zingone A;Ryan BM;Tsang JS;Biancotto A
通讯作者：
Biancotto A
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen
影响因子：
50.3
作者：
Calon A;Espinet E;Palomo-Ponce S;Tauriello DV;Iglesias M;Céspedes MV;Sevillano M;Nadal C;Jung P;Zhang XH;Byrom D;Riera A;Rossell D;Mangues R;Massagué J;Sancho E;Batlle E
通讯作者：
Batlle E
影响因子：
4.4
作者：
Carter H;Douville C;Stenson PD;Cooper DN;Karchin R
通讯作者：
Karchin R
影响因子：
3.7
作者：
Wolf Horrell EM;Boulanger MC;D'Orazio JA
通讯作者：
D'Orazio JA