Familial clustering of multiple sclerosis in a Dutch genetic isolate

Hoppenbrouwers, I A; Cortes, LM Pardo; Aulchenko, Yurii S.; Sintnicolaas, K.; Njajou, Omer T.; Snijders, Pieter J.L.M.; Oostra, Ben A.; Duijn, C.M. van; Hintzen, Rogier Q.

doi:10.1177/1352458506071216

Cited by 24 publications

(29 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Familial aggregation of MS has been recognized earlier [3,7,11]. Relatively recently, a study from the Netherlands suggested familial clustering in a genetically isolated population, wherein 24 of 48 MS patients could be linked to a common ancestor in 14 generations as a result of a high level of inbreeding [12]. Consanguineous marriages are widely practiced in Kuwait, which results in increased homozygosity [13].…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Multiple Sclerosis in Kuwait: A Population-Based Case-Control Study

et al. 2012

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a chronic and progressively disabling inflammatory autoimmune disorder of the central nervous system. MS has a multifactorial etiology and is triggered by environmental factors in individuals with complex genetic risk profiles. The epidemiology of MS changes with the spatial and temporal distribution of these genetic and nongenetic risk factors. This population-based matched case-control study aimed to determine the risk factors for MS in Kuwait. From May 2 to 9, 2010, we enrolled 101 confirmed MS cases using the list frame maintained by the Multiple Sclerosis Association of Kuwait. For each case, two population controls individually matched for age (±2 years), gender and nationality were selected. Data on demographic, socioeconomic variables, potential genetic and environmental factors were collected using a structured questionnaire. For a case, the questions were directed to the period that preceded the recognition of the disease, while for each of the two matched controls, a date of ‘pseudodiagnosis’ of MS was established, i.e. the date on which the control subject was of the same age as his/her matched case was at MS diagnosis and accordingly questions were directed to the preceding period. The multivariable conditional logistic regression model showed that compared with controls, the cases were significantly more likely to have a family history of MS [matched odds ratio (OR)_adj = 6.7; 95% confidence interval (95% CI): 2.5–18.0; p < 0.001] or have suffered from a head trauma in the past before MS diagnosis (matched OR_adj = 2.6; 95% CI: 1.2–5.5; p = 0.014). Furthermore, compared with controls, cases were significantly more likely to have stayed in Kuwait during the Iraqi invasion of 1990 (matched OR_adj = 1.8; 95% CI: 1.1–3.5; p = 0.022). This study showed that a family history of MS, a history of head injury, and presence in Kuwait at the time of the Iraqi invasion of 1990 were associated with a significantly increased MS risk. Future retrospective cohort studies by using existing biological and epidemiological databases may provide a clue to MS etiology.

show abstract

Section: Discussionmentioning

confidence: 99%

Risk Factors for Multiple Sclerosis in Kuwait: A Population-Based Case-Control Study

et al. 2012

View full text Add to dashboard Cite

show abstract

“…2 Originally, 48 MS patients (13 male, 35 female) were included. Later on, another female MS patient was identified and included.…”

Section: Participants From the Dutch Genetically Isolated Populationmentioning

confidence: 99%

“…Although most were originally diagnosed as sporadic MS patients, a total of 25 (51%) could be linked to an extended pedigree. 2 Three of the 49 MS patients were excluded from analysis because they were sisters of one MS patient. Clinical characteristics from the 46 MS patients who were included for analysis are described in Table 3a.…”

Section: Participants From the Dutch Genetically Isolated Populationmentioning

confidence: 99%

See 1 more Smart Citation

EVI5 is a risk gene for multiple sclerosis

Hoppenbrouwers

Aulchenko²,

Ebers

et al. 2008

Genes Immun

Self Cite

View full text Add to dashboard Cite

HLA-DRB1 is the major locus associated with risk for multiple sclerosis (MS). A recent genome-wide study showed three additional single-nucleotide polymorphisms (SNPs), within the IL2RA and IL7RA genes respectively, also to be associated with MS. Consistent association but lower significance was found for 13 other SNPs. In this study, we aimed to verify association of these SNPs with MS in 46 MS patients and 194 controls from a Dutch genetically isolated population. Apart from the human leukocyte antigen locus, the EVI5 gene on chromosome 1 was confirmed as a novel risk gene, with odds ratios (ORs) even higher than those from the MS Consortium (ORs 2.01 and 1.9; P ¼ 0.01). The risk effect of EVI5 was further validated for the general MS population in an independent set of 1318 MS patients from the Canadian Collaborative Project on the Genetic Susceptibility to MS. On the basis of the transmission disequilibrium testing, a weak but significant risk effect was observed (OR 1.15; P ¼ 0.03 and OR 1.15; P ¼ 0.04). This study confirms EVI5 as another risk locus for MS; however, much of the genetic basis of MS remains unidentified.

show abstract

“…A study in a Dutch isolate found MS patients to be significantly more related to each other than the control group, and more often inbred (82% compared with 36%). 21 Sadovnick et al 22 found the sibling recurrence rate of MS to be almost four times as high among offspring of consanguineous parents than among those of unrelated parents (8.0% compared with 2.3%). Evidence for the importance of a founder effect in explaining the high prevalence of MS in the Southern Ostrobothnian region of western Finland has been found, which is also consistent with a possible role of recessive effects in MS aetiology.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders

et al. 2011

View full text Add to dashboard Cite

There is strong evidence for both genetic and environmental risk factors comprising the aetiology of multiple sclerosis (MS). While much progress has been made in recent years in identifying common genetic variants using genome-wide association studies, alternative approaches have remained relatively neglected. The prevalence of MS in Orkney and Shetland is among the highest in the world. Previous studies have suggested that a higher degree of parental relatedness in these isolated communities may contribute to the high rates of MS, indicating that recessive effects have an important role in MS aetiology. The Northern Isles Multiple Sclerosis (NIMS) study investigated the potential role of genome-wide homozygosity in MS risk by genotyping 88 MS patients, 89 controls matched by age, sex and ancestry, and a further 89 controls matched for sex and ancestry, but passed the majority of lifetime risk of developing MS (470 years of age). Three participants were removed on the basis of pedigreegenomic anomalies (n¼263). Three measures of genome-wide homozygosity were generated for each individual, and association with MS was assessed using logistic regression models. No effect of genome-wide homozygosity was detected, indicating that inbreeding and consanguinity are not risk factors for MS in this population.

show abstract

Familial clustering of multiple sclerosis in a Dutch genetic isolate

Cited by 24 publications

References 29 publications

Risk Factors for Multiple Sclerosis in Kuwait: A Population-Based Case-Control Study

Risk Factors for Multiple Sclerosis in Kuwait: A Population-Based Case-Control Study

EVI5 is a risk gene for multiple sclerosis

Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders

Contact Info

Product

Resources

About