Exome sequencing and characterization of 49,960 individuals in the UK Biobank.
Exome sequencing and characterization of 49,960 individuals in the UK Biobank.
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DOI：
10.1038/s41586-020-2853-0
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发表时间：
2020-10
期刊：
影响因子：
64.8
通讯作者：
Baras A
中科院分区：
文献类型：
--
作者：
Van Hout CV;Tachmazidou I;Backman JD;Hoffman JD;Liu D;Pandey AK;Gonzaga-Jauregui C;Khalid S;Ye B;Banerjee N;Li AH;O'Dushlaine C;Marcketta A;Staples J;Schurmann C;Hawes A;Maxwell E;Barnard L;Lopez A;Penn J;Habegger L;Blumenfeld AL;Bai X;O'Keeffe S;Yadav A;Praveen K;Jones M;Salerno WJ;Chung WK;Surakka I;Willer CJ;Hveem K;Leader JB;Carey DJ;Ledbetter DH;Geisinger-Regeneron DiscovEHR Collaboration;Cardon L;Yancopoulos GD;Economides A;Coppola G;Shuldiner AR;Balasubramanian S;Cantor M;Regeneron Genetics Center;Nelson MR;Whittaker J;Reid JG;Marchini J;Overton JD;Scott RA;Abecasis GR;Yerges-Armstrong L;Baras A
英国生物库是一项对502，543人的前瞻性研究，结合了广泛的表型和基因型数据，为世界各地的研究人员提供了简化的访问。在这里，我们描述了前49，960名研究参与者的外显子组序列数据的发布，揭示了大约400万个编码变体（其中约98.6%的频率低于1%）。数据包括198，269个常染色体预测功能丧失（LOF）变体，与插补序列相比增加了14倍以上。几乎所有的基因（超过97%）都至少有一个携带LOF变异的携带者，大多数基因（超过69%）至少有十个携带LOF变异的携带者。我们通过对1,730种表型的关联分析，说明了在这一人群中表征LOF变异的能力。除了复制已建立的关联外，我们还发现了对疾病性状有很大影响的新型LOF变体，包括对静脉曲张的PIEZO 1，对角膜阻力的COL 6A 1，对骨密度的MEPE，以及对血细胞性状的IQGAP 2和GMPR。我们通过调查具有临床重要性的致病性变异的患病率进一步证明了外显子组测序的价值，并表明该人群中有2%具有医学上可操作的变异。此外，我们描述了致病性BRCA 1和BRCA 2变异体携带者的癌症发病率。来自前49，960名参与者的外显子组序列突出了基因组测序在大型人群研究中的前景，现在科学界可以使用。来自英国生物库的前49，960名参与者的外显子组序列突出了基因组测序在大规模人群研究中的前景，现在科学界可以访问。
The UK Biobank is a prospective study of 502,543 individuals, combining extensive phenotypic and genotypic data with streamlined access for researchers around the world. Here we describe the release of exome-sequence data for the first 49,960 study participants, revealing approximately 4 million coding variants (of which around 98.6% have a frequency of less than 1%). The data include 198,269 autosomal predicted loss-of-function (LOF) variants, a more than 14-fold increase compared to the imputed sequence. Nearly all genes (more than 97%) had at least one carrier with a LOF variant, and most genes (more than 69%) had at least ten carriers with a LOF variant. We illustrate the power of characterizing LOF variants in this population through association analyses across 1,730 phenotypes. In addition to replicating established associations, we found novel LOF variants with large effects on disease traits, including PIEZO1 on varicose veins, COL6A1 on corneal resistance, MEPE on bone density, and IQGAP2 and GMPR on blood cell traits. We further demonstrate the value of exome sequencing by surveying the prevalence of pathogenic variants of clinical importance, and show that 2% of this population has a medically actionable variant. Furthermore, we characterize the penetrance of cancer in carriers of pathogenic BRCA1 and BRCA2 variants. Exome sequences from the first 49,960 participants highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community. Exome sequences from the first 49,960 participants in the UK Biobank highlight the promise of genome sequencing in large population-based studies and are now accessible to the scientific community.
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影响因子：
16.6
作者：
Choquet H;Thai KK;Yin J;Hoffmann TJ;Kvale MN;Banda Y;Schaefer C;Risch N;Nair KS;Melles R;Jorgenson E
通讯作者：
Jorgenson E
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
影响因子：
3.3
作者：
Chaerkady R;Shao H;Scott SG;Pandey A;Jun AS;Chakravarti S
通讯作者：
Chakravarti S
DOI：
10.1038/gim.2013.73
发表时间：
2013-07
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1155/2014/724546
发表时间：
2014
期刊：
ISRN ophthalmology
影响因子：
--
作者：
Garcia-Porta N;Fernandes P;Queiros A;Salgado-Borges J;Parafita-Mato M;González-Méijome JM
通讯作者：
González-Méijome JM