Genome-wide association study identifies five risk loci for pernicious anemia
Open Access
- 17 June 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 12 (1), 1-9
- https://doi.org/10.1038/s41467-021-24051-6
Abstract
Pernicious anemia is a rare condition characterized by vitamin B12 deficiency anemia due to lack of intrinsic factor, often caused by autoimmune gastritis. Patients with pernicious anemia have a higher incidence of other autoimmune disorders, such as type 1 diabetes, vitiligo, and autoimmune thyroid issues. Therefore, the disease has a clear autoimmune basis, although the genetic susceptibility factors have thus far remained poorly studied. We conduct a genome-wide association study meta-analysis in 2166 cases and 659,516 European controls from population-based biobanks and identify genome-wide significant signals in or near the PTPN22 (rs6679677, p=1.91x10(-24), OR=1.63), PNPT1 (rs12616502, p=3.14x10(-8), OR=1.70), HLA-DQB1 (rs28414666, p=1.40x10(-16), OR=1.38), IL2RA (rs2476491, p=1.90x10(-8), OR=1.22) and AIRE (rs74203920, p=2.33x10(-9), OR=1.83) genes, thus providing robust associations between pernicious anemia and genetic risk factors. Pernicious anemia shows co-incidence with autoimmune disorders, yet the genetic basis for this condition is understudied. Here, the authors perform a genome-wide association study meta-analysis on pernicious anemia, identifying five susceptibility loci that map to genes with known roles in autoimmune disease.This publication has 52 references indexed in Scilit:
- Genetic Architecture of Vitamin B12 and Folate Levels Uncovered Applying Deeply Sequenced Large DatasetsPLoS Genetics, 2013
- Imputing Amino Acid Polymorphisms in Human Leukocyte AntigensPLOS ONE, 2013
- Seven newly identified loci for autoimmune thyroid diseaseHuman Molecular Genetics, 2012
- Bayesian refinement of association signals for 14 loci in 3 common diseasesNature Genetics, 2012
- Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes CasesPLoS Genetics, 2011
- Pernicious anemia – Genetic insightsAutoimmunity Reviews, 2011
- GWAMA: software for genome-wide association meta-analysisBMC Bioinformatics, 2010
- Rapid and Accurate Haplotype Phasing and Missing-Data Inference for Whole-Genome Association Studies By Use of Localized Haplotype ClusteringAmerican Journal of Human Genetics, 2007
- HLA-DR15 Haplotype and Multiple Sclerosis: A HuGE ReviewAmerican Journal of Epidemiology, 2007
- Risk of fractures in patients with pernicious anemiaJournal of Bone and Mineral Research, 1992