Amyotrophic lateral sclerosis is not linked to multiple sclerosis in a population based study

Background/Aims: Recent studies suggest that antecedent disease could impact the pathophysiology of the motoneuron disease Amyotrophic Lateral Sclerosis (ALS). We performed a case-control study to examine the prevalence of 11 antecedent diseases in ALS. Methods: Prevalence of antecedent disease in a 1,288 patient ALS population (Emory University ALS Clinic, Atlanta, Ga., USA) is compared to an age, gender, and geography-matched 7,561 subject control population using a statistical odds ratio (OR) with 95% confidence interval. Results: Association of ALS with odds of arthritis (OR = 0.14); non-ALS neurological disease (OR = 0.14); liver disease (OR = 0.19); chronic obstructive pulmonary disorder or COPD (OR = 0.23); kidney disease (OR = 0.32); adult asthma (OR = 0.39); diabetes (OR = 0.47); hypertension (OR = 0.56); obesity (OR = 0.6); hyperlipidemia or hypercholesterolemia (OR = 0.62); and thyroid disease (OR = 0.78). Conclusions: The prevalence of antecedent disease was overall less in the ALS population. We present two potential lines of inquiry to explain these results: (1) ‘Other disease as ALS protection' - antecedent diseases infer biochemical neuroprotection to ALS; (2) ‘ALS as other disease protection' - the underpinnings of ALS could infer protection to other diseases, possibly via the mechanism hypervigilant regulation or ‘too-high' regulatory feedback gains.

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“…However, these results generally support the findings of previous smaller studies examining individual diseases in ALS patients [e.g 1, 2, 6, 20…”

Section: Discussionsupporting

confidence: 91%

Antecedent Disease Is Less Prevalent in Amyotrophic Lateral Sclerosis

et al. 2015

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“…17 A population-based study of 810 ALS cases observed only 2 with a prior diagnosis of MS, which was believed to be no more than expected by chance, and neither had a C9orf72 GGGGCC repeat expansion. 18 This latter result would suggest that our findings in relation to MS and ALS may also be confounded by misdiagnosis.…”

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confidence: 77%

Autoimmune disease preceding amyotrophic lateral sclerosis

et al. 2013

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Objective: To study whether the risk of amyotrophic lateral sclerosis (ALS) is increased in people with prior autoimmune disease.Methods: An all-England hospital record-linkage dataset spanning 1999-2011 was used.Cohorts were constructed of people with each of a range of autoimmune diseases; the incidence of ALS in each disease cohort was compared with the incidence of ALS in a cohort of individuals without prior admission for the autoimmune disease.Results: There were significantly more cases than expected of ALS associated with a prior diagnosis of asthma, celiac disease, younger-onset diabetes (younger than 30 years), multiple sclerosis, myasthenia gravis, myxedema, polymyositis, Sjögren syndrome, systemic lupus erythematosus, and ulcerative colitis. Conclusions:

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“…Hence, C9orf72 variation does not appear to be a risk factor for MS. It has been suggested that MS can act as a modifier that increases the likelihood of C9orf72 expansions becoming penetrant and causing concurrent ALS (25), although further investigation is required (40).…”

Section: Discussionmentioning

confidence: 99%

No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

Setten

Diekstra

Ripke

et al. 2013

Human Molecular Genetics

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Genome-wide association studies have been successful in identifying common variants that influence the susceptibility to complex diseases. From these studies, it has emerged that there is substantial overlap in susceptibility loci between diseases. In line with those findings, we hypothesized that shared genetic pathways may exist between multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). While both diseases may have inflammatory and neurodegenerative features, epidemiological studies have indicated an increased co-occurrence within individuals and families. To this purpose, we combined genome-wide data from 4088 MS patients, 3762 ALS patients and 12 030 healthy control individuals in whom 5 440 446 single-nucleotide polymorphisms (SNPs) were successfully genotyped or imputed. We tested these SNPs for the excess association shared between MS and ALS and also explored whether polygenic models of SNPs below genome-wide significance could explain some of the observed trait variance between diseases. Genome-wide association meta-analysis of SNPs as well as polygenic analyses fails to provide evidence in favor of an overlap in genetic susceptibility between MS and ALS. Hence, our findings do not support a shared genetic background of common risk variants in MS and ALS.

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Amyotrophic lateral sclerosis is not linked to multiple sclerosis in a population based study

Cited by 8 publications

References 4 publications

Antecedent Disease Is Less Prevalent in Amyotrophic Lateral Sclerosis

Antecedent Disease Is Less Prevalent in Amyotrophic Lateral Sclerosis

Autoimmune disease preceding amyotrophic lateral sclerosis

No evidence for shared genetic basis of common variants in multiple sclerosis and amyotrophic lateral sclerosis

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