학술논문
Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps
Document Type
Report
Author
Iotchkova, Valentina; Huang, Jie; Morris, John A; Jain, Deepti; Barbieri, Caterina; Walter, Klaudia; Min, Josine L; Chen, Lu; Astle, William; Cocca, Massimilian; Deelen, Patrick; Elding, Heather; Farmaki, Aliki-Eleni; Franklin, Christopher S; Franberg, Mattias; Gaunt, Tom R; Hofman, Albert; Jiang, Tao; Kleber, Marcus E; Lachance, Genevieve; Luan, Jian'an; Malerba, Giovanni; Matchan, Angela; Mead, Daniel; Memari, Yasin; Ntalla, Ioanna; Panoutsopoulou, Kalliope; Pazoki, Raha; Perry, John R B; Rivadeneira, Fernando; Sabater-Lleal, Maria; Sennblad, Bengt; Shin, So-Youn; Southam, Lorraine; Traglia, Michela; van Dijk, Freerk; van Leeuwen, Elisabeth M; Zaza, Gianluigi; Zhang, Weihua; Amin, Najaf; Butterworth, Adam; Chambers, John C; Dedoussis, George; Dehghan, Abbas; Franco, Oscar H; Franke, Lude; Frontini, Mattia; Gambaro, Giovanni; Gasparini, Paolo; Hamsten, Anders; Issacs, Aaron; Kooner, Jaspal S; Kooperberg, Charles; Langenberg, Claudia; Marz, Winfried; Scott, Robert A; Swertz, Morris A; Toniolo, Daniela; Uitterlinden, Andre G; van Duijn, Cornelia M; Watkins, Hugh; Zeggini, Eleftheria; Maurano, Mathew T; Timpson, Nicholas J; Reiner, Alexander P; Auer, Paul L; Soranzo, Nicole
Source
Nature Genetics. November 2016, Vol. 48 Issue 11, p1303, 10 p.
Subject
Language
English
ISSN
1061-4036
Abstract
Author(s): Valentina Iotchkova [1, 2]; Jie Huang [2, 3]; John A Morris [4, 5]; Deepti Jain [6]; Caterina Barbieri [2, 7]; Klaudia Walter [2]; Josine L Min [8]; Lu Chen [...]
Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) [less than] 1%) or low-frequency (1% [less than] MAF [less than] 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.
Large-scale whole-genome sequence data sets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole-genome sequence data from the UK10K and 1000 Genomes Project into 35,981 study participants of European ancestry, followed by association analysis with 20 quantitative cardiometabolic and hematological traits. We describe 17 new associations, including 6 rare (minor allele frequency (MAF) [less than] 1%) or low-frequency (1% [less than] MAF [less than] 5%) variants with platelet count (PLT), red blood cell indices (MCH and MCV) and HDL cholesterol. Applying fine-mapping analysis to 233 known and new loci associated with the 20 traits, we resolve the associations of 59 loci to credible sets of 20 or fewer variants and describe trait enrichments within regions of predicted regulatory function. These findings improve understanding of the allelic architecture of risk factors for cardiometabolic and hematological diseases and provide additional functional insights with the identification of potentially novel biological targets.