Population- and individual-specific regulatory variation in Sardinia.
Population- and individual-specific regulatory variation in Sardinia.
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DOI：
10.1038/ng.3840
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发表时间：
2017-05
期刊：
影响因子：
30.8
通讯作者：
Montgomery SB
中科院分区：
文献类型：
--
作者：
Pala M;Zappala Z;Marongiu M;Li X;Davis JR;Cusano R;Crobu F;Kukurba KR;Gloudemans MJ;Reinier F;Berutti R;Piras MG;Mulas A;Zoledziewska M;Marongiu M;Sorokin EP;Hess GT;Smith KS;Busonero F;Maschio A;Steri M;Sidore C;Sanna S;Fiorillo E;Bassik MC;Sawcer SJ;Battle A;Novembre J;Jones C;Angius A;Abecasis GR;Schlessinger D;Cucca F;Montgomery SB
复杂性状的遗传研究主要确定了与非编码变异的关联。为了进一步确定调控变异的贡献，我们结合了来自撒丁岛的624个个体的全基因组和转录组数据，以确定影响基因表达和剪接的常见和罕见变异。共检测到21,183个表达型数量性状基因座（eQTL）和6,768个剪接型数量性状基因座（sQTL），其中包括619个新QTL。我们确定了高频率的QTL和证据的选择附近的基因参与疟疾抗性和多发性硬化症的风险增加，反映了撒丁岛的流行病学史。使用家族关系，我们确定了809个分离的表达离群值（中位数z得分为2.97），平均每个个体13.3个基因。离群基因富集了近端罕见变异，为研究大效应调控变异及其与性状的相关性提供了新的途径。我们的研究结果提供了对调控变异的影响及其与群体历史和个体遗传风险的关系的深入了解。
Genetic studies of complex traits have mainly identified associations with non-coding variants. To further determine the contribution of regulatory variation, we combined whole genome and transcriptome data for 624 individuals from Sardinia in order to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 novel QTLs. We identified high-frequency QTLs and evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z-score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.