Family-based genome-wide association study of leprosy in Vietnam
Autoři:
Chaima Gzara aff001; Monica Dallmann-Sauer aff003; Marianna Orlova aff003; Nguyen Van Thuc aff006; Vu Hong Thai aff006; Vinicius M. Fava aff003; Marie-Thérèse Bihoreau aff007; Anne Boland aff007; Laurent Abel aff001; Alexandre Alcaïs aff001; Erwin Schurr aff003; Aurélie Cobat aff001
Působiště autorů:
Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM UMR1163, Paris, France
aff001; Université de Paris, Imagine Institute, Paris, France
aff002; McGill International TB Centre, Montreal, QC, Canada
aff003; Program in Infectious Diseases and Immunity in Global Health, The Research Institute of the McGill University Health Centre, Montreal, QC, Canada
aff004; Department of Medicine and Human Genetics, Faculty of Medicine, McGill University, Montreal, QC, Canada
aff005; Hospital for Dermato-Venereology, District, Ho Chi Minh City, Vietnam
aff006; Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Evry, France
aff007; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, United States of America
aff008
Vyšlo v časopise:
Family-based genome-wide association study of leprosy in Vietnam. PLoS Pathog 16(5): e32767. doi:10.1371/journal.ppat.1008565
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.ppat.1008565
Souhrn
Leprosy is a chronic infectious disease of the skin and peripheral nerves with a strong genetic predisposition. Recent genome-wide approaches have identified numerous common variants associated with leprosy, almost all in the Chinese population. We conducted the first family-based genome-wide association study of leprosy in 622 affected offspring from Vietnam, followed by replication in an independent sample of 1181 leprosy cases and 668 controls of the same ethnic origin. The most significant results were observed within the HLA region, in which six SNPs displayed genome-wide significant associations, all of which were replicated in the independent case/control sample. We investigated the signal in the HLA region in more detail, by conducting a multivariate analysis on the case/control sample of 319 GWAS-suggestive HLA hits for which evidence for replication was obtained. We identified three independently associated SNPs, two located in the HLA class I region (rs1265048: OR = 0.69 [0.58–0.80], combined p-value = 5.53x10-11; and rs114598080: OR = 1.47 [1.46–1.48], combined p-value = 8.77x10-13), and one located in the HLA class II region (rs3187964 (OR = 1.67 [1.55–1.80], combined p-value = 8.35x10-16). We also validated two previously identified risk factors for leprosy: the missense variant rs3764147 in the LACC1 gene (OR = 1.52 [1.41–1.63], combined p-value = 5.06x10-14), and the intergenic variant rs6871626 located close to the IL12B gene (OR = 0.73 [0.61–0.84], combined p-value = 6.44x10-8). These results shed new light on the genetic control of leprosy, by dissecting the influence of HLA SNPs, and validating the independent role of two additional variants in a large Vietnamese sample.
Klíčová slova:
Genetic loci – Genome-wide association studies – Genomics statistics – Genotyping – Inflammatory bowel disease – Leprosy – Molecular genetics – Variant genotypes
Zdroje
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