Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants
Open accessAbstract
We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
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By 2011, common variants in 26 genomic loci had been associated with multiple sclerosis risk and independently replicated.
“by 2011, common variants in 26 genomic loci had been associated with MS risk and independently replicated”
From Genome‐wide association studies of multiple sclerosis (2018) · cites this paper as [33]
The Results (Association with nsSNPs; page unavailable) identify IL7R among genes with variants previously associated with MS, supporting the general point that genetic variants had been linked to MS risk. The Abstract (page unavailable) reports independent replication of two loci for ankylosing spondylitis, not MS. This 2007 paper does not support the claim that 26 MS loci had been independently replicated by 2011. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSome regions contain expected associations across diseases and traits; the association of the same common polymorphisms in IL23R in Crohn's disease, psoriasis, and ankylosing spondylitis points to a shared molecular cause.
“4) Some regions contain expected associations across diseases and traits. Crohn’s disease, psoriasis, and ankylosing spondylitis have long been recognized to share clinical features; the association of the same common polymorphisms in IL23R in all three diseases points to a shared molecular cause (96, 109, 110).”
From Genetic Mapping in Human Disease (2008) · cites this paper as [109]
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- Authors
- Wellcome Trust Case Control Consortium, & The Australo-Anglo-American Spondylitis Consortium (TASC)
- Venue
- Nature Genetics
- Published
- 2007-10-21
- Volume
- 39
- Issue
- 11
- Pages
- 1329-1337
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC2680141
- OpenAlex
- W2046579578
- Cited by
- 1,374
- References
- 51
- Citations by year
- 2026: 9 · 2025: 23 · 2024: 24 · 2023: 40 · 2022: 37 · 2021: 48 · 2020: 53 · 2019: 58 · 2018: 63 · 2017: 68 · 2016: 56 · 2015: 84 · 2014: 77 · 2013: 124 · 2012: 98
- FWCI
- 66.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Lirias (KU Leuven) (submittedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Bristol Research (University of Bristol) (submittedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Faculty of Health; Institute of Health and Biomedical Innovation
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Wellcome Trust (081682, 089989, 090532, 057097, 076113)
- Cancer Research UK (A4994)
- Multiple Sclerosis Society
- Versus Arthritis (/17552)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR046208, R01AR048465)
- National Center for Research Resources (UL1RR024148, M01RR000425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Rheumatology › Spondyloarthritis Studies and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- non-synonymous SNPs, autoimmunity, ankylosing spondylitis, autoimmune thyroid disease, multiple sclerosis, breast cancer, IL23R, TSHR, FCRL3, genetic susceptibility loci, seronegative spondyloarthropathy
- MeSH terms
- Aminopeptidases, Breast Neoplasms, Chromosome Mapping, Genetics, Population, Genotype, Haplotypes, Humans, Multiple Sclerosis, North America, Receptors, Immunologic, Spondylitis, Ankylosing, Thyroiditis, Autoimmune, Autoimmunity, Minor Histocompatibility Antigens, Linkage Disequilibrium, Case-Control Studies, Polymerase Chain Reaction, Receptors, Interleukin, Polymorphism, Single Nucleotide
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