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

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.