Dataset Information

Replication analysis of variants associated with multiple sclerosis risk.

ABSTRACT: Multiple Sclerosis (MS) is a complex chronic neurodegenerative disorder resulting from an autoimmune reaction against myelin. So far, many genetic variants have been reported to associate with MS risk however their association is inconsistent across different populations. Here we investigated the association of the most consistently reported genetic MS risk variants in the Kuwaiti MS population in a case-control study designs. Of the 94 reported MS risk variants four variants showed MS risk association in Arabs exome analysis (EVI5 rs11808092 p?=?0.0002; TNFRSF1A rs1800693 p?=?0.00003; MTHFR rs1801131 p?=?0.038; and CD58 rs1414273 p?=?0.00007). Replication analysis in Kuwaiti MS cases and healthy controls confirmed EVI5 rs11808092A (OR: 1.6, 95%CI: 1.19-2.16, p?=?0.002) and MTHFR rs1801131G (OR: 1.79, 95%CI: 1.3-2.36, p?=?0.001) as MS risk genetic factors, while TNFRSF1A rs1800693C had a marginal MS risk association (OR: 1.36, 95%CI: 1.04-1.78, p?=?0.025) in the Kuwaiti population. CD58 rs1414273 did not sustain risk association (p?=?0.37). In conclusion, EVI5 rs11808092A, TNFRSF1A rs1800693C and MTHFR rs1801131G are MS risk factors in the Kuwaiti population. Further investigations into their roles in MS pathogenesis and progression are merited.

SUBMITTER: Dashti M

PROVIDER: S-EPMC7193640 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Replication analysis of variants associated with multiple sclerosis risk.

Dashti Mohammad M Ateyah Khadijah K Alroughani Raed R Al-Temaimi Rabeah R

Scientific reports 20200430 1

Multiple Sclerosis (MS) is a complex chronic neurodegenerative disorder resulting from an autoimmune reaction against myelin. So far, many genetic variants have been reported to associate with MS risk however their association is inconsistent across different populations. Here we investigated the association of the most consistently reported genetic MS risk variants in the Kuwaiti MS population in a case-control study designs. Of the 94 reported MS risk variants four variants showed MS risk asso ...[more]

PMID: 32355262

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Project description:ObjectiveMultiple sclerosis (MS) is a multifactorial neurologic disease characterized by modest but tractable heritability. Genome-wide association studies have identified and/or validated multiple polymorphisms in approximately 16 genes associated with susceptibility. We aimed at investigating the aggregation of genetic MS risk markers in individuals by comparing multiple- and single-case families.MethodsA weighted log-additive integrative approach termed MS genetic burden (MSGB) was used to account for the well-established genetic variants from previous association studies and meta-analyses. The corresponding genetic burden and its transmission was analyzed in 1,213 independent MS families (810 sporadic and 403 multicase families).ResultsMSGB analysis demonstrated a higher aggregation of susceptibility variants in multicase compared to sporadic MS families. In addition, the aggregation of non-major histocompatibility complex single nucleotide polymorphisms depended neither on gender nor on the presence or absence of HLA-DRB1*15:01 alleles. Interestingly, although a greater MSGB in siblings of MS patients was associated with an increased risk of MS (odds ratio, 2.1; p = 0.001), receiver operating characteristic curves of MSGB differences between probands and sibs (area under the receiver operator curves, 0.57 [95% confidence interval, 0.53-0.61]) show that case-control status prediction of MS cannot be achieved with the currently available genetic data.InterpretationThe primary interest in the MSGB concept resides in its capacity to integrate cumulative genetic contributions to MS risk. This analysis underlines the high variability of family load with known common variants. This novel approach can be extended to other genetically complex diseases. Despite the emphasis on assembling large case-control datasets, multigenerational, multiaffected families remain an invaluable resource for advancing the understanding of the genetic architecture of complex traits.

Dataset Information

Replication analysis of variants associated with multiple sclerosis risk.

Publications

Replication analysis of variants associated with multiple sclerosis risk.

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