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High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

Authors: Eyre, S.; Bowes, J.; Diogo, D.; Lee, A.; Barton, A.; Martin, P.; Zhernakkova, A.; +41 Authors

High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

Abstract

Using the Immunochip custom SNP array, which was designed for dense genotyping of 186 loci identified through genome-wide association studies (GWAS), we analyzed 11,475 individuals with rheumatoid arthritis (cases) of European ancestry and 15,870 controls for 129,464 markers. We combined these data in a meta-analysis with GWAS data from additional independent cases (n = 2,363) and controls (n = 17,872). We identified 14 new susceptibility loci, 9 of which were associated with rheumatoid arthritis overall and five of which were specifically associated with disease that was positive for anticitrullinated peptide antibodies, bringing the number of confirmed rheumatoid arthritis risk loci in individuals of European ancestry to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci. Bioinformatic analyses generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations.

Countries
United Kingdom, Australia, United Kingdom, United States, Netherlands, Netherlands, United Kingdom, United Kingdom, Netherlands, United Kingdom, United Kingdom
Keywords

EXPRESSION, Male, Insecta, Arthropoda, Coronary-heart-disease, European Continental Ancestry Group, 610, Expression, Polymorphism, Single Nucleotide, Article, White People, Association, Arthritis, Rheumatoid, 1311 Genetics, Rheumatoid, 616, Animalia, Humans, CORONARY-HEART-DISEASE, Genetic Predisposition to Disease, Polymorphism, METAANALYSIS, Taxonomy, Autoantibodies, Oligonucleotide Array Sequence Analysis, Risk loci, Arthritis, Chromosome Mapping, Single Nucleotide, Biodiversity, ASSOCIATION, Interleukin-6 receptor, Metaanalysis, RISK LOCI, Coleoptera, INTERLEUKIN-6 RECEPTOR, Genetic Loci, Female, Dryopidae, Genome-Wide Association Study

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
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585
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