Annotation of GWAS loci by tissue-specific quantitative interaction proteomics

Novo Nordisk Foundation Center for Protein Research scientists in international collaboration team behind back-to-back articles published in this week’s Nature Genetics and Nature Methods on a new method for gene identification from Genome-wide association studies and applied it to the heart rhythm disorder QT-interval variation

Annotation of GWAS loci by tissue-specific quantitative interaction proteomics

Post.doc Alicia Lundby and Professor Jesper V. Olsen from Novo Nordisk Foundation Center for Protein Research (CPR) have in collaboration with a team of international researchers developed a new method for identification of genes crucial for repolarization of human hearts based on tissue-specific quantitative interaction proteomics for annotation of genetic loci identified in genome wide association studies (GWAS). Specifically they investigated interaction networks of proteins known to be involved in the heritable disease called Long QT Syndrome (LQTS). They identified new genes and proteins affecting the QT interval duration by integrating the identified protein interaction networks with GWAS data from 100,000 individuals on genetic variants associated with QT interval variation in the general population. The results were confirmed by knock-down experiments in zebrafish and electrophysiology in xenopus oocytes. The genetic results and the proteomics method are published as a pair of articles back-to-back this week in Nature Genetics and Nature Methods.

Nature Methods 11, 868–874 (2014) doi:10.1038/nmeth.2997

Alicia Lundby, Elizabeth J Rossin, Annette B Steffensen, Moshe Rav Acha, Christopher Newton-Cheh, Arne Pfeufer, Stacey N Lynch, The QT Interval International GWAS Consortium (QT-IGC), Søren-Peter Olesen, Søren Brunak, Patrick T Ellinor, J Wouter Jukema, Stella Trompet, Ian Ford, Peter W Macfarlane, Bouwe P Krijthe, Albert Hofman, André G Uitterlinden, Bruno H Stricker, Hendrik M Nathoe, Wilko Spiering, Mark J Daly, Folkert W Asselbergs, Pim van der Harst, David J Milan, Paul I W de Bakker, Kasper Lage & Jesper V Olsen.

Nat Genet. 2014 Aug; 46(8):826-36. doi: 10.1038/ng.3014. Epub 2014 Jun 22.

Dan E Arking, Sara L Pulit, Lia Crotti, Pim van der Harst, Patricia B Munroe, Tamara T Koopmann, Nona Sotoodehnia, Elizabeth J Rossin, Michael Morley, Xinchen Wang, Andrew D Johnson, Alicia Lundby, Jesper V Olsen, Kasper Lage, Peter J Schwartz, Stefan Kääb, Aravinda Chakravarti, Michael J Ackerman, Arne Pfeufer, Paul I W de Bakker & Christopher Newton-Cheh