Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations.
Identity-by-descent detection across 487,409 British samples reveals fine scale population structure and ultra-rare variant associations.
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DOI：
10.1038/s41467-020-19588-x
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发表时间：
2020-11-30
影响因子：
16.6
通讯作者：
Palamara PF
中科院分区：
文献类型：
--
作者：
Nait Saada J;Kalantzis G;Shyr D;Cooper F;Robinson M;Gusev A;Palamara PF
同源同源性(IBD)片段的检测提供了遗传关联性的基本衡量标准，并在广泛的分析中发挥着关键作用。我们开发了FastSMC，这是一种IBD检测算法，它结合了快速的启发式搜索和基于合并的精确似然计算。FastSMC能够对过去几千年内的IBD节段进行生物库规模的检测和测年。我们将FastSMC应用于487,409个英国生物库样本，并检测到过去1500年内由共享祖先传播的~2140亿个IBD片段，获得了英国遗传亲缘关系的细粒度图像。共同祖先的分享与地理距离密切相关，使基因组数据能够以45千米的中位误差定位样本的出生坐标。我们通过识别具有异常强烈共同祖先的基因座来寻找最近积极选择的证据，并检测到12个全基因组范围的显著信号。我们设计了一种基于IBD的表型和极罕见的功能丧失变异之间的关联测试，识别了7个血液相关性状中的29个关联信号。在生物库水平的基因组数据中，通过逐个相同的下降(IBD)片段准确地测量遗传相关性是具有挑战性的。作者提出了IBD方法FastSMC，当应用于英国生物库时，它给出了过去2000年英国遗传亲缘关系和进化史的详细图景。
Detection of Identical-By-Descent (IBD) segments provides a fundamental measure of genetic relatedness and plays a key role in a wide range of analyses. We develop FastSMC, an IBD detection algorithm that combines a fast heuristic search with accurate coalescent-based likelihood calculations. FastSMC enables biobank-scale detection and dating of IBD segments within several thousands of years in the past. We apply FastSMC to 487,409 UK Biobank samples and detect ~214 billion IBD segments transmitted by shared ancestors within the past 1500 years, obtaining a fine-grained picture of genetic relatedness in the UK. Sharing of common ancestors strongly correlates with geographic distance, enabling the use of genomic data to localize a sample’s birth coordinates with a median error of 45 km. We seek evidence of recent positive selection by identifying loci with unusually strong shared ancestry and detect 12 genome-wide significant signals. We devise an IBD-based test for association between phenotype and ultra-rare loss-of-function variation, identifying 29 association signals in 7 blood-related traits. Accurately measuring genetic relatedness by Identical-By-Descent (IBD) segments is challenging in biobank-level genome data. The authors present IBD method FastSMC, which when applied to the UK Biobank gives a detailed picture of genetic relatedness and evolutionary history in the UK over the past 2000 years.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1056/nejmsr1809937
发表时间：
2019-08-15
期刊：
The New England journal of medicine
影响因子：
--
作者：
All of Us Research Program Investigators;Denny JC;Rutter JL;Goldstein DB;Philippakis A;Smoller JW;Jenkins G;Dishman E
通讯作者：
Dishman E
影响因子：
9.8
作者：
Browning, Sharon R.;Browning, Brian L.
通讯作者：
Browning, Brian L.
影响因子：
9.8
作者：
Gusev, Alexander;Kenny, Eimear E.;Pe'er, Itsik
通讯作者：
Pe'er, Itsik
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