ArticleHuman molecular genetics2009
Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS.
Article in Human molecular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 4 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 4 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Variants in the IL7RA gene confer susceptibility to multiple sclerosis in Caucasians: evidence based on 9734 cases and 10436 controls.Scientific reports · 2017Pooled it
- Association between the IL7R T244I polymorphism and multiple sclerosis risk: a meta analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2016Pooled it
- Association between the IL7R T244I polymorphism and multiple sclerosis: a meta-analysis.Molecular biology reports · 2011Pooled it
- IL12A, MPHOSPH9/CDK2AP1 and RGS1 are novel multiple sclerosis susceptibility loci.Genes and immunity · 2010Pooled it
- The Polygenic Nature of Multiple Sclerosis: Genetic Variants, Immunological Modulation, and Environmental Connections.Endocrine, metabolic & immune disorders drug targets · 2025Review
- Functional Identification of Complement Factor D and Analysis of Its Expression during GCRV Infection in Grass Carp (International journal of molecular sciences · 2021Article
- Asparaginase treatment side-effects may be due to genes with homopolymeric Asn codons (Review-Hypothesis).International journal of molecular medicine · 2015Review
- Association study of four polymorphisms in the interleukin-7 receptor alpha gene with multiple sclerosis in Eastern Iran.Iranian journal of basic medical sciences · 2015Article
- Characterizing runs of homozygosity and their impact on risk for psychosis in a population isolate.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2014Article
- Increased power of mixed models facilitates association mapping of 10 loci for metabolic traits in an isolated population.Human molecular genetics · 2011Article
- Opposing effects of the HLA-DRB1*0301-DQB1*0201 haplotype on the risk for multiple sclerosis in diverse Arab populations in Israel.Genes and immunity · 2010Article
- The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression.PloS one · 2010Article
- Genome-wide association study in a high-risk isolate for multiple sclerosis reveals associated variants in STAT3 gene.American journal of human genetics · 2010Article
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Authors and funding
22 authors at 17 institutions in 6 countries.
Funding
Abstract
Large case-control genome-wide association studies primarily expose common variants contributing to disease pathogenesis with modest effects. Thus, alternative strategies are needed to tackle rare, possibly more penetrant alleles. One strategy is to use special populations with a founder effect and isolation, resulting in allelic enrichment. For multiple sclerosis such a unique setting is reported in Southern Ostrobothnia in Finland, where the prevalence and familial occurrence of multiple sclerosis (MS) are exceptionally high. Here, we have studied one of the best replicated MS loci, 5p, and monitored for haplotypes shared among 72 regional MS cases, the majority of which are genealogically distantly related. The haplotype analysis over the 45 Mb region, covering the linkage peak identified in Finnish MS families, revealed only modest association at IL7R (P = 0.04), recently implicated in MS, whereas most significant association was found with one haplotype covering the C7-FLJ40243 locus (P = 0.0001), 5.1 Mb centromeric of IL7R. The finding was validated in an independent sample from the isolate and resulted in an odds ratio of 2.73 (P = 0.000003) in the combined data set. The identified relatively rare risk haplotype contains C7 (complement component 7), an important player of the innate immune system. Suggestive association with alleles of the region was seen also in more heterogeneous populations. Interestingly, also the complement activity correlated with the identified risk haplotype. These results suggest that the MS predisposing locus on 5p is more complex than assumed and exemplify power of population isolates in the identification of rare disease alleles.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.