TY - JOUR
T1 - The UK10K project identifies rare variants in health and disease
AU - Walter, Klaudia
AU - Min, Josine L.
AU - Huang, Jie
AU - Crooks, Lucy
AU - Memari, Yasin
AU - McCarthy, Shane
AU - Perry, John R.B.
AU - Xu, Changjiang
AU - Futema, Marta
AU - Lawson, Daniel
AU - Iotchkova, Valentina
AU - Schiffels, Stephan
AU - Hendricks, Audrey E.
AU - Danecek, Petr
AU - Li, Rui
AU - Floyd, James
AU - Wain, Louise V.
AU - Barroso, Inês
AU - Humphries, Steve E.
AU - Hurles, Matthew E.
AU - Zeggini, Eleftheria
AU - Barrett, Jeffrey C.
AU - Plagnol, Vincent
AU - Richards, J. Brent
AU - Greenwood, Celia M.T.
AU - Timpson, Nicholas J.
AU - Durbin, Richard
AU - Bala, Senduran
AU - Clapham, Peter
AU - Coates, Guy
AU - Cox, Tony
AU - Daly, Allan
AU - Du, Yuanping
AU - Edkins, Sarah
AU - Ellis, Peter
AU - Flicek, Paul
AU - Guo, Xiaosen
AU - Guo, Xueqin
AU - Huang, Liren
AU - Jackson, David K.
AU - Joyce, Chris
AU - Keane, Thomas
AU - Kolb-Kokocinski, Anja
AU - Langford, Cordelia
AU - Li, Yingrui
AU - Liang, Jieqin
AU - Lin, Hong
AU - Liu, Ryan
AU - Breen, Gerome
AU - St Clair, David
AU - UK10K Consortium
PY - 2015/10/1
Y1 - 2015/10/1
N2 - The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.
AB - The contribution of rare and low-frequency variants to human traits is largely unexplored. Here we describe insights from sequencing whole genomes (low read depth, 7×) or exomes (high read depth, 80×) of nearly 10,000 individuals from population-based and disease collections. In extensively phenotyped cohorts we characterize over 24 million novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with levels of triglycerides (APOB), adiponectin (ADIPOQ) and low-density lipoprotein cholesterol (LDLR and RGAG1) from single-marker and rare variant aggregation tests. We describe population structure and functional annotation of rare and low-frequency variants, use the data to estimate the benefits of sequencing for association studies, and summarize lessons from disease-specific collections. Finally, we make available an extensive resource, including individual-level genetic and phenotypic data and web-based tools to facilitate the exploration of association results.
UR - http://www.scopus.com/inward/record.url?scp=84943182742&partnerID=8YFLogxK
U2 - 10.1038/nature14962
DO - 10.1038/nature14962
M3 - Article
C2 - 26367797
AN - SCOPUS:84943182742
SN - 0028-0836
VL - 526
SP - 82
EP - 90
JO - Nature
JF - Nature
IS - 7571
ER -