The genetic epidemiology of multiple sclerosis
The genetic epidemiology of multiple sclerosis
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DOI：
10.1016/j.jneuroim.2003.08.009
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发表时间：
2003-10-01
影响因子：
3.3
通讯作者：
Haines, JL
中科院分区：
文献类型：
--
作者：
Kenealy, SJ;Pericak-Vance, MA;Haines, JL
Linkage studies in complex diseases like multiple sclerosis, where the effects attributable to individual loci are modest, are critically dependent upon the number of families included. We have combined the raw genotyping data from all published genome linkage screens in multiple sclerosis and thereby performed a linkage analysis including 719 families studied with a weighted average of 359 microsatellite markers per family (range 257-453) providing an average marker separation of 10.2 cM. Linkage with genome-wide significance is confirmed in the HLA region on chromosome 6p21. In addition, two novel regions suggestive of linkage are seen (17q21 and 22q13). Our simulations would imply that the number of peaks with NPL scores greater than or equal to 2.1 exceeds the number expected by chance alone. (C) 2003 Elsevier B.V. All rights reserved.Multiple sclerosis (MS) is a debilitating immunological and neurodegenerative disorder. Epidemiological studies have provided overwhelming evidence of complex genetic susceptibility to MS. However, with the exception of the human leukocyte antigen (HLA) locus, genetic studies have failed to consistently identify significant linkage or association with genes that modulate MS disease expression. Numerous functional candidate gene studies, linkage genomic screens, and locational candidate gene studies have been performed in an attempt to identify additional loci. However, these methods have demonstrated insufficient power to consistently identify genes or epigenetic factors for MS. More current approaches integrate information from a variety of sources (e.g. consistent linkage data, gene expression profiling, and functional characterization studies) and utilize high throughput methods (e.g. genotyping high density markers, utilizing pooling schemes and performing new statistical analyses) in an attempt to overcome power issues. The following article presents a review of MS genetics research and a brief overview of methods that are currently being developed and utilized for fine localization of MS loci, such as the method employed in the Genetic Analysis of Multiple sclerosis in Europeans (GAMES) study that is presented elsewhere in this journal. It is the hope of researchers that these methods will lead to the identification of susceptibility genes for MS that aid in elucidating pathogenic mechanisms and potential therapeutic strategies for this debilitating disease. (C) 2003 Elsevier B.V. All rights reserved.
