ABSTRACT
INTRODUCTION: Applications to pharmacy programs are declining worldwide. Previous research suggests that positioning of recruitment material according to prospective students' preferences may increase interest in the profession and entry-to-practice programs. The aim of this study was to determine messaging preferences for the role of the pharmacist. METHODS: This was a best-worst choice survey conducted at one institution in one country. Participants included prospective students, current pharmacy students, and others representing the general public. Thirteen statements (plus one control) describing the role of the pharmacist were extracted from pharmacy program websites. Survey participants completed the best-worst choice analysis, and a conditional logit model was used to estimate statement preference coefficients. RESULTS: A total of 150 complete survey responses were collected. The top ranked statement was, "Pharmacists are health care professionals who are experts in medicines" and the least ranked statement was the control statement, "Pharmacists are experts in dispensing medications and counting tablets." No differences were observed between the different groups of survey respondents. Other highly ranked statements spoke to the expertise of the pharmacist and promoted a well-defined role. Catchy statements, such as "Pharmacists are medicines superheroes," were not ranked highly. CONCLUSIONS: This study found that current and prospective pharmacy students preferred descriptive and explicit messages that align with pharmacists' professional identity for promotion of the pharmacist's role.
Subject(s)
Education, Pharmacy , Pharmaceutical Services , Pharmacy , Humans , Pharmacists , Patient CareABSTRACT
BACKGROUND: There is increasing need for evidence-based data on reproduction for women with multiple sclerosis (MS). First-trimester (first 13 weeks) miscarriages are relatively common in the general population. It is therefore important to have information on the frequency with which this occurs in women with MS. METHODS: The Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS) is a prospective study on women with MS who are pregnant or actively trying to conceive. As far as we are aware, this is the first study on miscarriages for this population that takes into account each woman's entire pregnancy history (i.e. before and after the MS diagnosis as well as during enrollment in CANPREG-MS). RESULTS: There were 208 pregnancies during the study and 36 resulted in first-trimester miscarriage for a rate of 17.31%, within the expected range of 15%-20% for the general population. CONCLUSIONS: CANPREG-MS provides real world data that there does not appear to be an increase in first-trimester miscarriages for women with MS. This information will be helpful to women with MS and their healthcare providers.
Subject(s)
Abortion, Spontaneous , Multiple Sclerosis , Pregnancy , Female , Humans , Abortion, Spontaneous/epidemiology , Pregnancy Trimester, First , Prospective Studies , CanadaABSTRACT
We describe the case of identical twin boys who presented with low body weight despite excessive caloric intake. An evaluation of their fibroblasts showed elevated oxygen consumption and decreased mitochondrial membrane potential. Exome analysis revealed a de novo heterozygous variant in ATP5F1B, which encodes the ß subunit of mitochondrial ATP synthase (also called complex V). In yeast, mutations affecting the same region loosen coupling between the proton motive force and ATP synthesis, resulting in high rates of mitochondrial respiration. Expression of the mutant allele in human cell lines recapitulates this phenotype. These data support an autosomal dominant mitochondrial uncoupling syndrome with hypermetabolism. (Funded by the National Institutes of Health.).
Subject(s)
Mitochondrial Diseases , Mitochondrial Proton-Translocating ATPases , Oxidative Phosphorylation , Oxygen Consumption , Humans , Male , Adenosine Triphosphate/metabolism , Diseases in Twins/genetics , Diseases in Twins/metabolism , Fibroblasts/metabolism , Mitochondria/metabolism , Mitochondrial Diseases/congenital , Mitochondrial Diseases/genetics , Mitochondrial Diseases/metabolism , Mitochondrial Proton-Translocating ATPases/genetics , Mitochondrial Proton-Translocating ATPases/metabolism , Mutation , Oxygen Consumption/genetics , Oxygen Consumption/physiology , Twins, Monozygotic/geneticsABSTRACT
OBJECTIVE: To evaluate the impact of temporal increase of female to male (F:M) sex ratio for persons with multiple sclerosis (MS) on the familial risk (empiric recurrence risks or RRs) for biological relatives of affected individuals. METHODS: Detailed family histories were systematically obtained from people with MS attending the University of British Columbia Hospital MS Clinic. The study cohort was born in 1970 or more recently. Data were collected from 1 September 2015 to 31 January 2019. The study was designed to allow only one proband per family. Age-corrected RRs for biological relatives of probands were calculated based on a modification of the maximum-likelihood approach. RESULTS: Data analyses were possible for 746 unique probands (531 females; 215 males) and 19,585 of their biological relatives. RRs were temporally impacted. CONCLUSION: Both genetic sharing and environmental factors are important in determining RRs. It appears that there is an increase in MS risk due to environmental factors in later life (i.e. not shared family environment). Environmental exposures in genetically predisposed individuals might be driving the MS risk. The increase in F:M ratio of RRs for sisters/brothers of female probands over time is likely due to environmental differences.
Subject(s)
Multiple Sclerosis , Family , Female , Genetic Predisposition to Disease , Humans , Likelihood Functions , Male , Middle Aged , Multiple Sclerosis/epidemiology , Multiple Sclerosis/genetics , Risk , Risk Factors , Sex RatioABSTRACT
OBJECTIVE: The objective of this prospective "real world" study is to gain insight into the different "roads to conception" that women with MS take as part of the prospective Canadian Multiple Sclerosis Pregnancy Study (CANPREG-MS). METHODS: Participants are women with MS who are planning a pregnancy. Data cut-off for analyses was April 30, 2020. RESULTS: We believe this is the first prospective National study of women with MS planning pregnancies.The data are for the first 44 women enrolled of whom 26 achieved pregnancy by cut-off date. Seven women used assisted reproductive technologies (ARTs); 6 stopped disease modifying therapy (DMT) against their neurologists' recommendations; 6 had an interruption(s) in trying to conceive due to MS relapses, MRI-detected inflammation, or limited "windows of opportunity" between DMT courses. CONCLUSION: The study illustrates the roads that women take to conception, even if they are on the same therapy and have similar clinical expression of MS. Advice given by treating neurologists on washout periods show discrepancies. This paper highlights the real problem that there is no definitive, international consensus on managing these women due to the lack of "real world" data and thus the goal of CANPREG-MS is to provide such real world data.
ABSTRACT
Multiple sclerosis (MS) is an inflammatory disease of the central nervous system characterized by myelin loss and neuronal dysfunction. Although the majority of patients do not present familial aggregation, Mendelian forms have been described. We performed whole-exome sequencing analysis in 132 patients from 34 multi-incident families, which nominated likely pathogenic variants for MS in 12 genes of the innate immune system that regulate the transcription and activation of inflammatory mediators. Rare missense or nonsense variants were identified in genes of the fibrinolysis and complement pathways (PLAU, MASP1, C2), inflammasome assembly (NLRP12), Wnt signaling (UBR2, CTNNA3, NFATC2, RNF213), nuclear receptor complexes (NCOA3), and cation channels and exchangers (KCNG4, SLC24A6, SLC8B1). These genes suggest a disruption of interconnected immunological and pro-inflammatory pathways as the initial event in the pathophysiology of familial MS, and provide the molecular and biological rationale for the chronic inflammation, demyelination and neurodegeneration observed in MS patients.
Subject(s)
Genetic Predisposition to Disease , Inflammation/genetics , Multiple Sclerosis/genetics , Transcriptome/genetics , Adult , Codon, Nonsense , Demyelinating Diseases/genetics , Demyelinating Diseases/pathology , Exome/genetics , Female , Humans , Inflammation/metabolism , Inflammation/pathology , Male , Middle Aged , Multiple Sclerosis/metabolism , Multiple Sclerosis/pathology , Myelin Sheath/genetics , Myelin Sheath/pathology , Nerve Degeneration/genetics , Nerve Degeneration/pathology , Neurons/metabolism , Neurons/pathology , Pedigree , Exome Sequencing , Young AdultABSTRACT
BACKGROUND: Studies have indicated an association between low Ultraviolet B (UVB) exposure and an increased risk of developing multiple sclerosis (MS). Few studies, however, have explored whether UVB exposure is associated with the age at MS symptom onset. OBJECTIVE: We investigated the potential association between cumulative early life ambient UVB exposure and age at MS onset, using satellite data to measure ambient UVB exposure. METHODS: Adult onset MS patients were selected from the University of British Columbia's MS genetic database (1980-2005). Patients' places of residence from birth to age 18 years were geocoded (latitude and longitude) and assigned UVB values using NASA's Total Ozone Mapping Spectrometer (TOMS) dataset. Linear regression was used to explore the relationship between cumulative UVB exposure (measured for age periods 0-6, 7-12, 13-18, 0-12, and 0-18) and age at MS onset. RESULTS: 3226 patients were included in the analysis. Of these, 74% were female, with an overall mean symptom onset age of 33.3 years. At onset, a total of 2944 (91%) had a relapsing-remitting disease course, 254 (8%) had primary progressive and the disease course for 28 (1%) was unknown. No significant associations between cumulative early life ambient UVB exposure and age at MS onset were observed. Patient sex, MS phenotype, and immigration to Canada after age 18 were significantly associated with age of onset (pâ¯<â¯0.01). CONCLUSIONS: Early life ambient UVB, as measured by satellite imagery, was not significantly associated with the age at MS onset.
Subject(s)
Multiple Sclerosis, Chronic Progressive/epidemiology , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Ultraviolet Rays , Adult , Age of Onset , Cohort Studies , Female , Geographic Mapping , Humans , Linear Models , Male , Multivariate Analysis , Risk Factors , Spacecraft , Spectrum Analysis/instrumentationABSTRACT
The implementation of exome sequencing technologies has started to unravel the genetic etiology of familial multiple sclerosis (MS). A homozygote p.G587S mutation in NLRP1 has been suggested as potentially causative for the onset of MS in an affected sibling pair, who later developed malignant melanoma. To validate the proposed role of recessive NLRP1 mutations in the pathological mechanisms of MS, we examined exome sequencing data from 326 MS patients from Canada for the identification of NLRP1 missense and nonsense variants. This analysis did not identify the previously described p.G587S mutation; however, three patients with potential NLRP1 compound heterozygote mutations were observed. Haplotype and segregation analyses indicate that the variants observed in these patients were inherited in cis, and do not segregate with disease within families. Thus, the analysis of MS patients from Canada failed to identify potentially pathogenic mutations in NLRP1, including the previously described p.G587S mutation. Further studies are necessary to confirm a role of NLRP1 in the pathophysiology of MS.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Apoptosis Regulatory Proteins/genetics , Exome/genetics , Genetic Predisposition to Disease , Multiple Sclerosis/genetics , Adult , Codon, Nonsense , Female , Genotype , Haplotypes , Heterozygote , Homozygote , Humans , Male , Middle Aged , Multiple Sclerosis/physiopathology , Mutation, Missense/genetics , NLR Proteins , Pedigree , Exome SequencingABSTRACT
The genetic contribution to clinical outcomes for multiple sclerosis (MS) has yet to be defined. We performed exome sequencing analysis in 100 MS patients presenting opposite extremes of clinical phenotype (discovery cohort), and genotyped variants of interest in 2016 MS patients (replication cohort). Linear and logistic regression analyses were used to identify significant associations with disease course, severity and onset. Our analysis of the discovery cohort nominated 38 variants in 21 genes. Replication analysis identified PSMG4 p.W99R and NLRP5 p.M459I to be associated with disease severity (p=0.002 and 0.008). CACNA1H p.R1871Q was found associated with patients presenting relapsing remitting MS at clinical onset (p=0.028) whereas NLRP5 p.M459I and EIF2AK1 p.K558R were associated with primary progressive disease (p=0.031 and 0.023). In addition, PSMG4 p.W99R and NLRP5 p.R761L were found to correlate with an earlier age at MS clinical onset, and MC1R p.R160W with delayed onset of clinical symptoms (p=0.010-0.041).
Subject(s)
Autoantigens/genetics , Multiple Sclerosis/genetics , Adult , Age of Onset , Calcium Channels, T-Type/genetics , Disease Progression , Exome/genetics , Female , Genotype , Humans , Male , Middle Aged , Mitochondrial Proteins , Nuclear Proteins , Phenotype , Receptor, Melanocortin, Type 1/genetics , Severity of Illness Index , Young Adult , eIF-2 Kinase/geneticsABSTRACT
Objective Chronic cerebrospinal venous insufficiency (CCSVI) has been hypothesized to be a risk factor for multiple sclerosis (MS). Venoplasty has been proposed as a treatment for CCSVI. The aim of our study was to gain a better understanding of the "real-world" safety and longitudinal effectiveness of venoplasty Methods: British Columbia residents who self-reported having had venoplasty and consented to participate in the study were interviewed and followed for up to 24 months post-therapy using standardized structured questionnaires Results: Participants reported procedure-related complications (11.5%) and complications within the first month after the procedure (17.3%). Initially, more than 40% of participants perceived that the venoplasty had had positive effects on their health conditions, such as fatigue, numbness, balance, concentration/memory and mobility. However, this improvement was not maintained over time Conclusions: Follow-up patient-reported outcomes indicated that the initial perception of the positive impact of venoplasty on the health conditions of MS patients was not sustained over time. In addition, venoplasty was not without associated morbidity.
Subject(s)
Angioplasty , Patient Satisfaction , Registries , Self Report , Venous Insufficiency/epidemiology , Venous Insufficiency/surgery , Aged , Anastomosis, Surgical/methods , Angioplasty/methods , British Columbia/epidemiology , Chronic Disease , Female , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/diagnosis , Multiple Sclerosis, Relapsing-Remitting/epidemiology , Multiple Sclerosis, Relapsing-Remitting/surgery , Treatment Outcome , Venous Insufficiency/diagnosisABSTRACT
Genetic variants in the purinergic receptors P2RX4 and P2RX7 have been shown to affect susceptibility to multiple sclerosis (MS). In this study, we set out to evaluate whether rare coding variants of major effect could also be identified in these purinergic receptors. Sequencing analysis of P2RX4 and P2RX7 in 193 MS patients and 100 controls led to the identification of a rare three variant haplotype (P2RX7 rs140915863:C>T [p.T205M], P2RX7 rs201921967:A>G [p.N361S], and P2RX4 rs765866317:G>A [p.G135S]) segregating with disease in a multi-incident family with six family members diagnosed with MS (logarithm of odds = 3.07). Functional analysis of this haplotype in HEK293 cells revealed impaired P2X7 surface expression (P < 0.01), resulting in over 95% inhibition of adenosine triphosphate (ATP)-induced pore function (P < 0.001) and a marked reduction in phagocytic ability (P < 0.05). In addition, transfected cells showed 40% increased peak ATP-induced inward current (P < 0.01), and a greater Ca2+ response to the P2X4 135S variant compared with wild type (P < 0.0001). Our study nominates rare genetic variants in P2RX4 and P2RX7 as major genetic contributors to disease, further supporting a role for these purinergic receptors in MS and the disruption of transmembrane cation channels leading to impairment of phagocytosis as the pathological mechanisms of disease.
Subject(s)
Genetic Predisposition to Disease , Multiple Sclerosis/genetics , Receptors, Purinergic P2X4/genetics , Receptors, Purinergic P2X7/genetics , Female , HEK293 Cells , Haplotypes , Humans , Male , Multiple Sclerosis/pathology , Polymorphism, Single NucleotideABSTRACT
Several single-gene disorders with clinical and radiological characteristics similar to those observed in multiple sclerosis (MS) patients have been described. To evaluate whether this phenotypic overlap can be ascribed to a common genetic etiology, 28 genes known to present pathogenic mutations for 24 of these disorders were sequenced in 270 MS patients. All identified variants were genotyped in 2131 MS cases and 830 healthy controls, and those exclusively observed in patients were assessed for segregation within families. This analysis identified 9 rare variants in 6 genes segregating with disease in 13 families. Four different mutations were identified in CYP27A1, including a reported pathogenic mutation for cerebrotendinous xanthomatosis (p.R405W), which was observed in six patients from a multi-incident family, three diagnosed with MS, two with an undefined neurological disease and one seemingly healthy. A LYST p.V1678A and a PDHA1 p.K387Q mutation were both observed in five MS patients from three separate multi-incident families. In addition, CLCN2 p.V174G, GALC p.D162E and POLG p.R361G were each identified in two MS patients from one family. This study suggests a shared genetic etiology between MS and the characterized single-gene disorders, and highlights cholesterol metabolism and the synthesis of oxysterols as important biological mechanisms for familial MS.
Subject(s)
Genetic Diseases, Inborn , Multiple Sclerosis/genetics , Amino Acid Sequence , Animals , Cholestanetriol 26-Monooxygenase/genetics , Exome , Female , Humans , Male , Pedigree , Sequence Homology, Amino AcidABSTRACT
Identifying rare genetic variants that drive the onset of disease is challenging, even before considering the additional genetic and environmental influences that likely exist in complex diseases. We recently published a study proposing a rare variant in the NR1H3 gene (p.R415Q, rs61731956) as responsible for the onset of multiple sclerosis (MS) in two multi-incident families (Wang et al., 2016). This publication has generated much discussion, and fortunately the possibility to validate a finding or prove it spurious can occur rapidly in genetic studies. All novel discoveries must be replicated, and best efforts should be made to ensure that these replications use the appropriate samples and approach, and provide the correct interpretation of the results. This Matters Arising Response paper addresses the Minikel and MacArthur (2016) and The International Multiple Sclerosis Genetics Consortium (2016) Matters Arising papers, published concurrently in Neuron.
Subject(s)
Genetic Predisposition to Disease , Genetic Variation , Alleles , Case-Control Studies , Humans , Multiple Sclerosis/geneticsABSTRACT
Multiple sclerosis (MS) is an inflammatory disease characterized by myelin loss and neuronal dysfunction. Despite the aggregation observed in some families, pathogenic mutations have remained elusive. In this study, we describe the identification of NR1H3 p.Arg415Gln in seven MS patients from two multi-incident families presenting severe and progressive disease, with an average age at onset of 34 years. Additionally, association analysis of common variants in NR1H3 identified rs2279238 conferring a 1.35-fold increased risk of developing progressive MS. The p.Arg415Gln position is highly conserved in orthologs and paralogs, and disrupts NR1H3 heterodimerization and transcriptional activation of target genes. Protein expression analysis revealed that mutant NR1H3 (LXRA) alters gene expression profiles, suggesting a disruption in transcriptional regulation as one of the mechanisms underlying MS pathogenesis. Our study indicates that pharmacological activation of LXRA or its targets may lead to effective treatments for the highly debilitating and currently untreatable progressive phase of MS.
Subject(s)
Liver X Receptors/genetics , Multiple Sclerosis, Chronic Progressive/genetics , Adult , Case-Control Studies , Female , Gene Expression/genetics , Genetic Predisposition to Disease/genetics , Humans , Male , Middle Aged , Mutation , Pedigree , Phenotype , Protein Isoforms/geneticsABSTRACT
Multiple sclerosis (MS) is a prevalent neurological disease of complex etiology. Here, we describe the characterization of a multi-incident MS family that nominated a rare missense variant (p.G420D) in plasminogen (PLG) as a putative genetic risk factor for MS. Genotyping of PLG p.G420D (rs139071351) in 2160 MS patients, and 886 controls from Canada, identified 10 additional probands, two sporadic patients and one control with the variant. Segregation in families harboring the rs139071351 variant, identified p.G420D in 26 out of 30 family members diagnosed with MS, 14 unaffected parents, and 12 out of 30 family members not diagnosed with disease. Despite considerably reduced penetrance, linkage analysis supports cosegregation of PLG p.G420D and disease. Genotyping of PLG p.G420D in 14446 patients, and 8797 controls from Canada, France, Spain, Germany, Belgium, and Austria failed to identify significant association with disease (P = 0.117), despite an overall higher prevalence in patients (OR = 1.32; 95% CI = 0.93-1.87). To assess whether additional rare variants have an effect on MS risk, we sequenced PLG in 293 probands, and genotyped all rare variants in cases and controls. This analysis identified nine rare missense variants, and although three of them were exclusively observed in MS patients, segregation does not support pathogenicity. PLG is a plausible biological candidate for MS owing to its involvement in immune system response, blood-brain barrier permeability, and myelin degradation. Moreover, components of its activation cascade have been shown to present increased activity or expression in MS patients compared to controls; further studies are needed to clarify whether PLG is involved in MS susceptibility.
Subject(s)
Chromosomes, Human, Pair 6/chemistry , Multiple Sclerosis/genetics , Plasminogen/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Amino Acid Sequence , Case-Control Studies , Chromosomes, Human, Pair 6/metabolism , Exome , Female , Gene Expression , Genotype , Humans , Male , Middle Aged , Multiple Sclerosis/pathology , Pedigree , Risk Factors , Sequence Alignment , Sequence Homology, Amino AcidABSTRACT
Oxysterols produced by CH25H during cholesterol metabolism have been shown to play an important role in the immune response. In this study we report the genetic characterization of CH25H in patients diagnosed with multiples sclerosis (MS) or neuromyelitis optica (NMO), for the identification of genetic variants affecting disease susceptibility and course. Exome analysis in 212 MS and 14 NMO patients identified a rare CH25H p.Q17H mutation in two NMO patients of Asian ancestry. In addition, association analysis of common CH25H variants identified a nominally significant association with MS patients presenting a clinical course consistent with primary progressive disease.
Subject(s)
Genetic Predisposition to Disease/genetics , Multiple Sclerosis/genetics , Neuromyelitis Optica/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Aged , DNA Mutational Analysis , Female , Humans , Male , Middle Aged , Multiple Sclerosis/metabolism , Neuromyelitis Optica/metabolismABSTRACT
BACKGROUND: Global variation in the incidence of multiple sclerosis (MS) is generally ascribed to differences in genetic and environmental risk factors. Here we investigate temporal trends in the incidence of MS and related disorders in British Columbia, Canada, from 1986 to 2010, focusing particularly on the Asian ethnic subpopulation. METHODS: A longitudinal database was screened to identify newly diagnosed cases of MS and related disorders, including neuromyelitis optica and clinically isolated syndromes. Age-standardized, sex-specific mean annual incidence was calculated for the Asian and non-Asian population of British Columbia for 5-year intervals from 1986 to 2010. Temporal changes and cohort differences in incidence rates and demographic characteristics were evaluated. RESULTS: During this period, the incidence of MS and related disorders in the non-Asian population remained relatively unchanged, from 10.41 (95% confidence interval [CI]: 9.87-10.97) to 9.91 (95% CI: 9.46-10.39) per 100,000 (p=0.167). In contrast, incidence in the Asian population doubled during the same period. This increase was driven by a precipitous rise in the incidence of MS in females from 0.71 (95% CI: 0.01-1.50) to 2.08 (95% CI: 1.43-2.91) per 100,000 (p=0.004), including both Canadian-born and immigrant Asians. The incidence of neuromyelitis optica did not change significantly during this period. CONCLUSIONS: The incidence of MS may be increasing among females in the Asian ethnic population of British Columbia.
Subject(s)
Asian/statistics & numerical data , Multiple Sclerosis/epidemiology , Adult , Age of Onset , Aged , British Columbia/epidemiology , Databases, Factual , Emigrants and Immigrants , Female , Humans , Incidence , Male , Middle Aged , Multiple Sclerosis/complications , Neuromyelitis Optica/epidemiology , Sex Factors , Socioeconomic FactorsABSTRACT
Background. A population-based prevalent cohort of 150 clinical definite multiple sclerosis (MS) cases (102 women; 48 men) ascertained on January 1, 1977, Saskatoon, Saskatchewan, was found to have a familial rate of MS as 17.3%. Objectives. To determine the occurrence of familial MS cases and the frequency of MS among the biological relatives of the study cohort. Methods. The search for new familial cases MS affected relatives continued for 35 years until 2012. The natural history of the disease of sporadic cases is compared with that of the familial cases. SPSS V19 and Kaplan-Meier survival analysis were used for data analysis. Results. Of the 150 unrelated MS patients, 49 cases (32.7%) (36 women and 13 men) were reported of having at least one family member with MS. There were a total of 86 affected relatives, 26 (30.2%) first-degree relatives, 15 (17.4%) second-degree relatives, 20 (23.3%) third-degree relatives, and 25 (29.1%) distant relatives. The average age of MS onset for men with sporadic MS was 33.9 (SD = 10) years and 27.6 (SD = 8.4) years for familial cases and 29.3 (SD = 8.3) years and 26.8 (SD = 8.5) years for women. Conclusion. This 35-year longitudinal natural history study reveals a high frequency of cases with family members developing MS and supports a genetic influence in the etiology of MS.