Genome-wide association study identifies five risk loci for pernicious anemia
Triin Laisk, Maarja Lepamets, Mariann Koel, Erik Abner, Andres Metspalu, Mari Nelis, Lili Milani, Tõnu Esko, Reedik Mägi
Abstract
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 = 1.91 × 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.