The genetics of multiple sclerosis: an update 2010.
Multiple sclerosis (MS) is a chronic neuro-inflammatory autoimmune disease believed to arise from complex interactions of both environmental and genetic factors. The successful accomplishment of genome-wide association studies (GWAS), analyzing >100.000 single nucleotide polymorphism markers simultaneously based on chip technology, has recently brought interesting new insights into the genetic background of this complex disease. To date, six GWAS have been performed for MS; even though study design and results vary substantially between experiments, some new susceptibility genes have been identified and replicated using this approach. For example, nucleotide variation in the interleukin 7 receptor (IL7RA), the interleukin 2 receptor (IL2RA), the CD58 and the c-type lectin domain family 16 member A (CLEC16A) genes has been consistently associated with MS in several populations. There appears to be substantial overlap between susceptibility variants for different autoimmune diseases, suggesting that at least part of the genetic background may be shared among autoimmune disorders. Regarding phamacogenomics, results from GWAS for treatment response to interferon beta (IFNb) in MS suggest that genes that code for neurotransmitter-gated channels might play a role in the drug response. In particular, GPC5 has already been confirmed to be an IFNb response gene in an independent study. Future prospects include, among others, more sophisticated analyses of GWAS data, advances in the 'one SNP at a time' approach towards pathway and network-based analyses, next-generation sequencing techniques as well as studies of gene/gene and gene/environment interactions.
Hoffjan
Sabine
S
Department of Human Genetics, Ruhr-University, Universitätsstrasse 150, 44801 Bochum, Germany. sabine.hoffjan@ruhr-uni-bochum.de
Akkad
Denis A
DA
D000818:Animals; D018968:CD58 Antigens / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D037181:Lectins, C-Type / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D020395:Receptors, Interleukin-7 / Q000235:genetics
D018968:CD58 Antigens; C522505:CLEC16A protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D009004:Monosaccharide Transport Proteins; D020395:Receptors, Interleukin-7