ArticleAmerican journal of human genetics2010
Evolutionary and functional analysis of celiac risk loci reveals SH2B3 as a protective factor against bacterial infection.
Article in American journal of human genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 4 of them syntheses that pooled it.
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Who cites it
96 citing papers in PubMed, 4 syntheses or guidelines pooled it, 196 citations in OpenAlex.
- Genome-wide association study of colorectal cancer identifies six new susceptibility loci.Nature communications · 2015Pooled it
- Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci.Nature communications · 2015Pooled it
- Meta-analysis in more than 17,900 cases of ischemic stroke reveals a novel association at 12q24.12.Neurology · 2014Pooled it
- Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility.World journal of gastroenterology · 2014Pooled it
- Fast pairwise coalescence enables gene-resolution scans for recent selection in diverse human populations.bioRxiv : the preprint server for biology · 2026Article
- Gut mucosal immune responses - Implications for celiac disease and food allergy.Seminars in immunology · 2025Review
- Biallelic SH2B3 germline variants are associated with a neonatal myeloproliferative disease and multisystemic involvement.European journal of human genetics : EJHG · 2025Article
- Early human migration determines the risk of being attacked by wolves: ethnic gene diversity on the development of systemic lupus erythematosus.Journal of rheumatic diseases · 2024Review
- Genetic history of Cambridgeshire before and after the Black Death.Science advances · 2024Article
- From an understanding of etiopathogenesis to novel therapies-what is new in the treatment of celiac disease?Frontiers in pharmacology · 2024Review
- Cystatin C is glucocorticoid responsive, directs recruitment of Trem2+ macrophages, and predicts failure of cancer immunotherapy.Cell genomics · 2023Article
- Celiac Disease and the Risk of Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- Biallelic deleterious germlineEJHaem · 2023Article
- The adaptive evolution of cancer driver genes.BMC genomics · 2023Article
- CTLA4, SH2B3, and CLEC16A diversely affect the progression of early islet autoimmunity in relatives of Type 1 diabetes patients.Clinical and experimental immunology · 2023Article
- Genetic adaptation to pathogens and increased risk of inflammatory disorders in post-Neolithic Europe.Cell genomics · 2023Article
- Prioritizing autoimmunity risk variants for functional analyses by fine-mapping mutations under natural selection.Nature communications · 2022Article
- COVID-19 and systemic lupus erythematosus genetics: A balance between autoimmune disease risk and protection against infection.PLoS genetics · 2022Article
- Review
- 1,000 ancient genomes uncover 10,000 years of natural selection in Europe.bioRxiv : the preprint server for biology · 2022Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 9 institutions in 5 countries.
Funding
Abstract
Celiac disease (CD) is an intolerance to dietary proteins of wheat, barley, and rye. CD may have substantial morbidity, yet it is quite common with a prevalence of 1%-2% in Western populations. It is not clear why the CD phenotype is so prevalent despite its negative effects on human health, especially because appropriate treatment in the form of a gluten-free diet has only been available since the 1950s, when dietary gluten was discovered to be the triggering factor. The high prevalence of CD might suggest that genes underlying this disease may have been favored by the process of natural selection. We assessed signatures of selection for ten confirmed CD-associated loci in several genome-wide data sets, comprising 8154 controls from four European populations and 195 individuals from a North African population, by studying haplotype lengths via the integrated haplotype score (iHS) method. Consistent signs of positive selection for CD-associated derived alleles were observed in three loci: IL12A, IL18RAP, and SH2B3. For the SH2B3 risk allele, we also show a difference in allele frequency distribution (Fst) between HapMap phase II populations. Functional investigation of the effect of the SH2B3 genotype in response to lipopolysaccharide and muramyl dipeptide revealed that carriers of the SH2B3 rs3184504*A risk allele showed stronger activation of the NOD2 recognition pathway. This suggests that SH2B3 plays a role in protection against bacteria infection, and it provides a possible explanation for the selective sweep on SH2B3, which occurred sometime between 1200 and 1700 years ago.
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