Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.
Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.
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DOI：
10.1093/hmg/ddac243
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发表时间：
2023-03-06
影响因子：
3.5
通讯作者：
中科院分区：
文献类型：
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作者：
多基因评分（PGS）可以识别有不良健康事件风险的个体，并指导基于遗传学的个性化医疗。然而，目前尚不清楚PGS在不同人群之间的翻译效果如何，这限制了它们在经过充分研究的种族中的应用。蛋白质是将遗传易感性和环境因素与疾病联系起来的中间性状，许多血液循环中的蛋白质水平代表了疾病相关过程的功能读数。我们假设，研究欧洲和阿拉伯人群之间一整套血液循环蛋白的遗传结构，可以为PGS在未充分研究人群中的可翻译性提供新的线索。因此，我们使用基于SOMAscan适配体的亲和蛋白质组学平台在卡塔尔生物银行的2935个样本中测量的1301个蛋白质，利用全基因组测序数据进行了全基因组关联研究，并评估了来自欧洲研究的蛋白质数量性状（pqtl）在阿拉伯人群中的复制。然后，我们研究了两个种群之间共享pQTL信号的共定位。最后，我们比较了欧洲和阿拉伯队列中来自高加索人群的蛋白质PGS的表现。我们发现大部分共享的pQTL信号（81.8%）在两个种群之间共定位。大约三分之一的遗传蛋白遗传性可以用来自欧洲队列的蛋白质PGS来解释，与阿拉伯人相比，欧洲人的蛋白质PGS表现好20%。我们的研究结果与将PGS转化为非高加索人群以及将基因研究扩展到未充分研究人群的未来努力相关。
Polygenic scores (PGS) can identify individuals at risk of adverse health events and guide genetics-based personalized medicine. However, it is not clear how well PGS translate between different populations, limiting their application to well-studied ethnicities. Proteins are intermediate traits linking genetic predisposition and environmental factors to disease, with numerous blood circulating protein levels representing functional readouts of disease-related processes. We hypothesized that studying the genetic architecture of a comprehensive set of blood-circulating proteins between a European and an Arab population could shed fresh light on the translatability of PGS to understudied populations. We therefore conducted a genome-wide association study with whole-genome sequencing data using 1301 proteins measured on the SOMAscan aptamer-based affinity proteomics platform in 2935 samples of Qatar Biobank and evaluated the replication of protein quantitative traits (pQTLs) from European studies in an Arab population. Then, we investigated the colocalization of shared pQTL signals between the two populations. Finally, we compared the performance of protein PGS derived from a Caucasian population in a European and an Arab cohort. We found that the majority of shared pQTL signals (81.8%) colocalized between both populations. About one-third of the genetic protein heritability was explained by protein PGS derived from a European cohort, with protein PGS performing ~20% better in Europeans when compared to Arabs. Our results are relevant for the translation of PGS to non-Caucasian populations, as well as for future efforts to extend genetic research to understudied populations.
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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：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
4.5
作者：
Al Kuwari, Hanan;Al Thani, Asma;Elliott, Paul
通讯作者：
Elliott, Paul
影响因子：
30.8
作者：
Bulik-Sullivan B;Finucane HK;Anttila V;Gusev A;Day FR;Loh PR;ReproGen Consortium;Psychiatric Genomics Consortium;Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3;Duncan L;Perry JR;Patterson N;Robinson EB;Daly MJ;Price AL;Neale BM
通讯作者：
Neale BM
DOI：
10.1093/bioinformatics/btq419
发表时间：
2010-09-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Pruim RJ;Welch RP;Sanna S;Teslovich TM;Chines PS;Gliedt TP;Boehnke M;Abecasis GR;Willer CJ
通讯作者：
Willer CJ