Germline Mutations in <i>CIDEB</i> and Protection against Liver Disease
Niek Verweij, Mary E. Haas, Jonas B. Nielsen, Olukayode Sosina, Minhee Kim, Parsa Akbari, Tanima De, George Hindy, Jonas Bovijn, Trikaldarshi Persaud, Lawrence Miloscio, Mary Germino, Lampros Panagis, Kyoko Watanabe, Joelle Mbatchou, Marcus B. Jones, Michelle G. LeBlanc, Suganthi Balasubramanian, Craig Lammert, Sofia Enhörning, Olle Melander, David J. Carey, Christopher D. Still, Tooraj Mirshahi, Daniel J. Rader, Prodromos Parasoglou, Johnathon R. Walls, John D. Overton, Jeffrey G. Reid, Aris N. Economides, Michael Cantor, Brian Zambrowicz, Andrew Murphy, Gonçalo R. Abecasis, Manuel A. R. Ferreira, Ēriks Šmagris, Viktoria Gusarova, Mark W. Sleeman, George D. Yancopoulos, Jonathan Marchini, Hyun Min Kang, Katia Karalis, Alan R. Shuldiner, Giusy Della Gatta, Adam E. Locke, Aris Baras, Luca A. Lotta
Abstract
BACKGROUND: Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets. METHODS: We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations. RESULTS: small interfering RNA knockdown prevented the buildup of large lipid droplets. CONCLUSIONS: conferred substantial protection from liver disease. (Funded by Regeneron Pharmaceuticals.).