Journal
NATURE
Volume 506, Issue 7488, Pages 376-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/nature12873
Keywords
-
Categories
Funding
- National Institutes of Health (NIH) [R01-AR057108, R01-AR056768, U01-GM092691, R01-AR059648]
- Burroughs Wellcome Fund
- Japan Society of the Promotion of Science
- Australian National Health and Medical Research Council [1036541]
- Netherlands Organization for Scientific Research
- Dutch Reumafonds [11-1-101]
- Rosalind Franklin Fellowship, University of Groningen
- Korea Healthcare technology R&D project, Ministry for Health and Welfare [A121983]
- RETICS program
- RIER
- Instituto de Salud Carlos III, Health Ministry [RD12/0009]
- Medical Biobank of Northern Sweden
- NIH (NIAMS) [R01-AR056768, R01-AR056291, R01-AR065944, P60 AR047785, R21 AR056042]
- European Research Council
- NIH [R01AR063759-01A1, K08-KAR055688A]
- National Health and Medical Research Foundation Senior Principal Research Fellowship
- Queensland State Government Premier's Fellowship
- China Ministry of Science and Technology [2011CB946100]
- National Natural Science Foundation of China [30972339, 81020108029, 81273283]
- Science and Technology Commission of Shanghai Municipality [08XD1400400, 11410701600, 10JC1418400]
- Canada Research Chair
- Sherman Family Chair in Genomics Medicine
- Canadian Institutes for Health Research [79321]
- Ontario Research Fund [05-075]
- Health and Labour Sciences Research Grants
- Ministry of Education, Culture, Sports, Science and Technology of the Japanese government
- BE THE CURE (BTCure) project
- Grants-in-Aid for Scientific Research [221S0001, 25293225, 22133008, 24592285, 24390360, 23229007] Funding Source: KAKEN
Ask authors/readers for more resources
A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available