TY - JOUR AU - Glicksberg, Benjamin S. AU - Amadori, Letizia AU - Akers, Nicholas K. AU - Sukhavasi, Katyayani AU - Franzén, Oscar AU - Li, Li AU - Belbin, Gillian M. AU - Akers, Kristin L. AU - Shameer, Khader AU - Badgeley, Marcus A. AU - Johnson, Kipp W. AU - Readhead, Ben AU - Darrow, Bruce J. AU - Kenny, Eimear E. AU - Betsholtz, Christer AU - Ermel, Raili AU - Skogsberg, Josefin AU - Ruusalepp, Arno AU - Schadt, Eric E. AU - Dudley, Joel T. AU - Ren, Hongxia AU - Kovacic, Jason C. AU - Giannarelli, Chiara AU - Li, Shuyu D. AU - Björkegren, Johan L. M. AU - Chen, Rong PY - 2019 DA - 2019/07/25 TI - Integrative analysis of loss-of-function variants in clinical and genomic data reveals novel genes associated with cardiovascular traits JO - BMC Medical Genomics SP - 108 VL - 12 IS - 6 AB - Genetic loss-of-function variants (LoFs) associated with disease traits are increasingly recognized as critical evidence for the selection of therapeutic targets. We integrated the analysis of genetic and clinical data from 10,511 individuals in the Mount Sinai BioMe Biobank to identify genes with loss-of-function variants (LoFs) significantly associated with cardiovascular disease (CVD) traits, and used RNA-sequence data of seven metabolic and vascular tissues isolated from 600 CVD patients in the Stockholm-Tartu Atherosclerosis Reverse Network Engineering Task (STARNET) study for validation. We also carried out in vitro functional studies of several candidate genes, and in vivo studies of one gene. SN - 1755-8794 UR - https://doi.org/10.1186/s12920-019-0542-3 DO - 10.1186/s12920-019-0542-3 ID - Glicksberg2019 ER -