Genome-wide association study identifies five risk loci for pernicious anemia

• Published in: Nature communications Vol. 12; no. 1; p. 3761
• Main Authors: Laisk, Triin, Lepamets, Maarja, Koel, Mariann, Abner, Erik, Mägi, Reedik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 45/43; 631/208/205/2138; 692/308/2056; 692/699/249/1313; Adult; Aged; AIRE Protein; Anemia; Anemia, Pernicious - genetics; Autoimmune diseases; Autoimmune Diseases - genetics; Diabetes mellitus (insulin dependent); Exoribonucleases - genetics; Female; Gastritis; Gastritis - pathology; Genes; Genetic Predisposition to Disease - genetics; Genetic Variation - genetics; Genome-wide association studies; Genome-Wide Association Study; Genomes; Histocompatibility antigen HLA; HLA-DQ beta-Chains - genetics; Humanities and Social Sciences; Humans; Interleukin 2 receptors; Interleukin-2 Receptor alpha Subunit - genetics; Loci; Male; Middle Aged; multidisciplinary; Pernicious anemia; Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics; Protein-tyrosine-phosphatase; Risk analysis; Risk Factors; Science; Science (multidisciplinary); Susceptibility; Thyroid; Transcription Factors - genetics; Vitamin B12; Vitamin deficiency; Vitiligo
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-24051-6

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  = 1.91 × 10 −24 , OR = 1.63 ) , PNPT1 (rs12616502, p  = 3.14 × 10 −8 , OR = 1.70), HLA-DQB1 (rs28414666, p  = 1.40 × 10 −16 , OR = 1.38), IL2RA (rs2476491, p  = 1.90 × 10 −8 , OR = 1.22) and AIRE (rs74203920, p  = 2.33 × 10 −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.