However, some of these MR results may be biased by horizontal pleiotropy with the proteins affecting multiple diseases,85 possibly via immune, renal and metabolic disease pathways,85-87 which subsequently contribute to the risk of dementia.85 There was also evidence from previous studies indicating higher levels of EDA2R were associated a smaller total brain volume, smaller grey matter volume, and less normal-appearing white matter volume.86 This evidence concerns the gene EDA2R and Other metabolic disease.