TY  - JOUR
A1  - Van Hout, Cristopher V.
A1  - Tachmazidou, Ioanna
A1  - Backman, Joshua D.
A1  - Hoffman, Joshua D.
A1  - Liu, Daren
A1  - Pandey, Ashutosh K.
A1  - Gonzaga-Jauregui, Claudia
A1  - Khalid, Shareef
A1  - Ye, Bin
A1  - Banerjee, Nilanjana
A1  - Li, Alexander H.
A1  - O'Dushlaine, Colm
A1  - Marcketta, Anthony
A1  - Staples, Jeffrey
A1  - Schurmann, Claudia
A1  - Hawes, Alicia
A1  - Maxwell, Evan
A1  - Barnard, Leland
A1  - Lopez, Alexander
A1  - Penn, John
A1  - Habegger, Lukas
A1  - Blumenfeld, Andrew L.
A1  - Bai, Xiaodong
A1  - O'Keeffe, Sean
A1  - Yadav, Ashish
A1  - Praveen, Kavita
A1  - Jones, Marcus
A1  - Salerno, William J.
A1  - Chung, Wendy K.
A1  - Surakka, Ida
A1  - Willer, Cristen J.
A1  - Hveem, Kristian
A1  - Leader, Joseph B.
A1  - Carey, David J.
A1  - Ledbetter, David H.
A1  - Cardon, Lon
A1  - Yancopoulos, George D.
A1  - Economides, Aris
A1  - Coppola, Giovanni
A1  - Shuldiner, Alan R.
A1  - Balasubramanian, Suganthi
A1  - Cantor, Michael
A1  - Nelson, Matthew R.
A1  - Whittaker, John
A1  - Reid, Jeffrey G.
A1  - Marchini, Jonathan
A1  - Overton, John D.
A1  - Scott, Robert A.
A1  - Abecasis, Goncalo R.
A1  - Yerges-Armstrong, Laura M.
A1  - Baras, Aris
T1  - Exome sequencing and characterization of 49,960 individuals in the UK Biobank
JF  - Nature : the international weekly journal of science
N2  - 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(1). 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, includingPIEZO1on varicose veins,COL6A1on corneal resistance,MEPEon bone density, andIQGAP2andGMPRon 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 pathogenicBRCA1andBRCA2variants. 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. <br /> 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.
KW  - clinical exome
KW  - breast-cancer
KW  - mutations
KW  - recommendations
KW  - gene
KW  - metaanalysis
KW  - variants,
KW  - BRCA1
KW  - risk
KW  - susceptibility
Y1  - 2020
U6  - https://doi.org/10.1038/s41586-020-2853-0
SN  - 0028-0836
SN  - 1476-4687
VL  - 586
IS  - 7831
SP  - 749
EP  - 756
PB  - Macmillan Publishers Limited
CY  - London
ER  -