Local Ancestry Adjusted Allelic Association Analysis Robustly Captures Tuberculosis Susceptibility Loci.

Autor:	Swart Y; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Uren C; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa., van Helden PD; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Hoal EG; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Möller M; DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.; Centre for Bioinformatics and Computational Biology, Stellenbosch University, Stellenbosch, South Africa.
Jazyk:	angličtina
Zdroj:	Frontiers in genetics [Front Genet] 2021 Oct 15; Vol. 12, pp. 716558. Date of Electronic Publication: 2021 Oct 15 (Print Publication: 2021).
DOI:	10.3389/fgene.2021.716558
Abstrakt:	Pulmonary tuberculosis (TB), caused by Mycobacterium tuberculosis , is a complex disease. The risk of developing active TB is in part determined by host genetic factors. Most genetic studies investigating TB susceptibility fail to replicate association signals particularly across diverse populations. South African populations arose because of multi-wave genetic admixture from the indigenous KhoeSan, Bantu-speaking Africans, Europeans, Southeast Asian-and East Asian populations. This has led to complex genetic admixture with heterogenous patterns of linkage disequilibrium and associated traits. As a result, precise estimation of both global and local ancestry is required to prevent both false positive and false-negative associations. Here, 820 individuals from South Africa were genotyped on the SNP-dense Illumina Multi-Ethnic Genotyping Array (∼1.7M SNPs) followed by local and global ancestry inference using RFMix. Local ancestry adjusted allelic association (LAAA) models were utilized owing to the extensive genetic heterogeneity present in this population. Hence, an interaction term, comprising the identification of the minor allele that corresponds to the ancestry present at the specific locus under investigation, was included as a covariate. One SNP (rs28647531) located on chromosome 4q22 was significantly associated with TB susceptibility and displayed a SNP minor allelic effect (G allele, frequency = 0.204) whilst correcting for local ancestry for Bantu-speaking African ancestry ( p -value = 5.518 × 10 -7 ; OR = 3.065; SE = 0.224). Although no other variants passed the significant threshold, clear differences were observed between the lead variants identified for each ancestry. Furthermore, the LAAA model robustly captured the source of association signals in multi-way admixed individuals from South Africa and allowed the identification of ancestry-specific disease risk alleles associated with TB susceptibility that have previously been missed. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Swart, Uren, van Helden, Hoal and Möller.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu