02069nas a2200361   4500000000100000008004100001260003400042100001700076700001500093700001200108700001500120700001600135700001600151700001100167700001500178700001300193700001300206700001400219700001500233700001300248700001400261700001000275700001200285700001900297700001700316700001400333700001100347700001500358700001200373245009200385856007500477520115500552       2022                            d  bCold Spring Harbor Laboratory1 aGilchrist JJ1 aAuckland K1 aParks T1 aMentzer AJ1 aGoldblatt L1 aNaranbhai V1 aBand G1 aRockett KA1 aToure OB1 aKonate S1 aSissoko S1 aDjimdé AA1 aThera MA1 aDoumbo OK1 aSow S1 aFloyd S1 aPönnighaus JM1 aWarndorff DK1 aCrampin A1 aFine P1 aFairfax BP1 aHill AV00aACTR1A has pleiotropic effects on risk of leprosy, inflammatory bowel disease and atopy  uhttps://www.medrxiv.org/content/10.1101/2022.01.31.22270046v1.full.pdf3 a<p>Leprosy remains a leading cause of infectious disability globally. Human genetic variation is a major determinant of susceptibility to infection, including leprosy. Large-scale genetic association studies have been pivotal in advancing our understanding of leprosy biology. These studies have been performed in Chinese, Vietnamese and Indian populations, and it remains unclear whether these insights are informative of leprosy susceptibility in African populations. To address this, we performed a genome-wide association study of leprosy susceptibility in Malawi and Mali. In doing so we replicate known leprosy susceptibility loci at MHC class I and II, LACC1 and SLC29A3. Furthermore, we identify a novel leprosy susceptibility locus, which modifies expression of ACTR1A in CD4+ T cells and demonstrates pleiotropy with inflammatory bowel disease (IBD) and atopic disease. These data deepen our understanding of leprosy biology, identifying ACTR1A expression in CD4+ T cells as a determinant of leprosy disease risk, and further define the role of this ancient pathogen in the evolution of immune-mediated diseases in modern populations.</p>