Incidence of Amyotrophic Lateral Sclerosis Among American Indians and Alaska Natives

Gordon, Paul H.; Mehal, Jason M.; Holman, Robert C.; Rowland, Lewis P.; Rowland, Andrew S.; Cheek, James E.

doi:10.1001/jamaneurol.2013.929

Cited by 33 publications

(13 citation statements)

References 26 publications

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“…Clinically, the disease predominantly affects upper and lower motor neurons, although impairment of extramotor systems – such as temporal, behavioral and executive frontal circuits – has also been reported suggesting that ALS should be better considered a multisystem disorder (Phukan et al, 2007; Goldstein and Abrahams, 2013). Progressive spinal muscular atrophy and primary lateral sclerosis have been classified as restricted phenotypes of ALS (10% of cases) but a clear separation is still controversial (Gordon et al, 2013). Isolated bulbar involvement (5%) and association with cognitive/behavioral signs that fulfill the diagnostic criteria of frontotemporal dementia (FTD) (5–15%) (Strong et al, 2017) underline the heterogeneity of the disease that also involves the age at onset, the rate of progression and finally the overall prognosis, thus drawing a complex scenario of the ALS phenotypes (Swinnen and Robberecht, 2014).…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis

Liguori

Nuzziello

Introna

et al. 2018

Front. Mol. Neurosci.

110

106

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Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurodegenerative disease. While genetics and other factors contribute to ALS pathogenesis, critical knowledge is still missing and validated biomarkers for monitoring the disease activity have not yet been identified. To address those aspects we carried out this study with the primary aim of identifying possible miRNAs/mRNAs dysregulation associated with the sporadic form of the disease (sALS). Additionally, we explored miRNAs as modulating factors of the observed clinical features. Study included 56 sALS and 20 healthy controls (HCs). We analyzed the peripheral blood samples of sALS patients and HCs with a high-throughput next-generation sequencing followed by an integrated bioinformatics/biostatistics analysis. Results showed that 38 miRNAs (let-7a-5p, let-7d-5p, let-7f-5p, let-7g-5p, let-7i-5p, miR-103a-3p, miR-106b-3p, miR-128-3p, miR-130a-3p, miR-130b-3p, miR-144-5p, miR-148a-3p, miR-148b-3p, miR-15a-5p, miR-15b-5p, miR-151a-5p, miR-151b, miR-16-5p, miR-182-5p, miR-183-5p, miR-186-5p, miR-22-3p, miR-221-3p, miR-223-3p, miR-23a-3p, miR-26a-5p, miR-26b-5p, miR-27b-3p, miR-28-3p, miR-30b-5p, miR-30c-5p, miR-342-3p, miR-425-5p, miR-451a, miR-532-5p, miR-550a-3p, miR-584-5p, miR-93-5p) were significantly downregulated in sALS. We also found that different miRNAs profiles characterized the bulbar/spinal onset and the progression rate. This observation supports the hypothesis that miRNAs may impact the phenotypic expression of the disease. Genes known to be associated with ALS (e.g., PARK7, C9orf72, ALS2, MATR3, SPG11, ATXN2) were confirmed to be dysregulated in our study. We also identified other potential candidate genes like LGALS3 (implicated in neuroinflammation) and PRKCD (activated in mitochondrial-induced apoptosis). Some of the downregulated genes are involved in molecular bindings to ions (i.e., metals, zinc, magnesium) and in ions-related functions. The genes that we found upregulated were involved in the immune response, oxidation–reduction, and apoptosis. These findings may have important implication for the monitoring, e.g., of sALS progression and therefore represent a significant advance in the elucidation of the disease’s underlying molecular mechanisms. The extensive multidisciplinary approach we applied in this study was critically important for its success, especially in complex disorders such as sALS, wherein access to genetic background is a major limitation.

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Section: Introductionmentioning

confidence: 99%

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis

Liguori

Nuzziello

Introna

et al. 2018

Front. Mol. Neurosci.

110

106

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“…Traditionally, randomized controlled trial (RCT) studies are the gold standard for inferring the causal impact of exposure on outcome. However, determining the causal relationship between premorbid BMI and ALS through RCT is challenging and unrealistic, because RCT necessarily requires a very large set of subjects and an extremely long follow-up before clinical manifest of ALS due to its rarity in the population [40] and wide variations in prevalence and incidence across various age groups [41, 42, 43, 44]. Therefore, it is desirable to investigate the causal association between premorbid BMI and ALS through observational studies.…”

Section: Introductionmentioning

confidence: 99%

Association between premorbid body mass index and amyotrophic lateral sclerosis: causal inference through genetic approaches

Zeng

2019

Preprint

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19Background: Inverse association between premorbid body mass index (BMI) and 20 amyotrophic lateral sclerosis (ALS) has been discovered in observational studies; 21 however, whether this association is causal remains largely unknown. 22 Methods: We employed a two-sample Mendelian randomization approach to evaluate 23 the causal relationship of genetically increased BMI with the risk of ALS. The 24 analyses were implemented using summary statistics obtained for the independent 25 instruments identified from large-scale genome-wide association studies of BMI (up 26 to ~770,000 individuals) and ALS (up to ~81,000 individuals). The causal relationship 27 between BMI and ALS was estimated using inverse-variance weighted methods and 28 was further validated through extensive complementary and sensitivity analyses. 29Findings: Using 1,031 instruments strongly related to BMI, the causal effect of per 30 one standard deviation increase of BMI was estimated to be 1.04 (95% CI 0.97~1.11, 31 p=0.275) in the European population. The null association between BMI and ALS 32 discovered in the European population also held in the East Asian population and was 33 robust against various modeling assumptions and outlier biases. Additionally, the 34 Egger-regression and MR-PRESSO ruled out the possibility of horizontal pleiotropic 35 effects of instruments. 36 Interpretation: Our results do not support the causal role of genetically increased or 37 decreased BMI on the risk of ALS. 38 Key words 39 Body mass index, Amyotrophic lateral sclerosis, Mendelian randomization, 40 Instrumental variable, Genome-wide association studies 41 3/23 1. Introduction 42 Amyotrophic lateral sclerosis (ALS) is a frequent adult-onset fatal neurodegenerative 43 disease clinically characterized by rapidly progressive motor neurons degeneration 44 and death because of respiratory failure [1]. Although great advance has been made 45for the understanding of ALS in the past decades, the pathogenic mechanism 46 underlying ALS remains largely unknown and only few therapeutic options can be 47 50 development of ALS [5, 6, 7, 8, 9, 10, 11]. However, no replicable and definitive 51 environmental risk factors are currently well established for ALS. In addition, due to 52 the quickly growing ageing of the population in the upcoming years, it is evaluated 53 that the number of ALS cases across globe will increase by about 70% [12], which is 54 anticipated to result in rather serious socioeconomic and health burden. Therefore, 55 understanding the risk factors of ALS for improving the medical intervention and 56 quality of life for ALS patients is considerably important from both disease treatment 57 and public health perspectives. 58 Among extensive epidemiological researches of ALS, an interesting and surprising 59 observation is that ALS patients often encounter a loss of weight or a decrease of body 60 mass index (BMI) at the early phase of diagnosis with many possible explanations [1, 61 13, 14, 15, 16, 17, 18, 19, 20]. Indeed, substan...

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“…Low physician-to-patient ratios, few neurologists, and vast geographic areas suggest that some patients with encephalitis might not seek medical care or receive a correct diagnosis. 32 Conversely, because there is no specific test for encephalitis, and the clinical presentation can be non-specific, it is also possible that some of the hospitalization records for the general U.S population incorrectly list an encephalitis-associated ICD-9-CM code in patients with mental status changes of other cause, thus inflating the estimates. In other neurologic diseases, under-ascertainment affects elderly women most prominently 33,34 ; a pattern of lower rates in women was not found in this study, suggesting that there are other factors contributing to our findings.…”

Section: Discussionmentioning

confidence: 99%

Encephalitis-Associated Hospitalizations among American Indians and Alaska Natives

Mehal

Holman²,

Vora³

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Encephalitis produces considerable morbidity in the United States, but morbidity rates among American Indian/Alaska Native (AI/AN) people have not been described. Hospitalization records listing an encephalitis diagnosis were analyzed by using Indian Health Service direct/contract inpatient data. For 1998-2010, there were 436 encephalitisassociated hospitalizations among AI/AN people, an average annual age-adjusted hospitalization rate of 3.1/100,000 population. The rate for infants (11.9) was more than double that for any other age group. Death occurred for 4.1% of hospitalizations. Consistent with reports for the general U.S. population, the rate was high among infants and most (53.9%) hospitalizations were of unexplained etiology. The average annual rate during the study period appeared lower than for the general U.S. population, due particularly to lower rates in the elderly. Future community-based surveillance and mortality studies are needed to confirm these findings and examine reasons underlying the low rates of encephalitis in AI/AN people.

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Incidence of Amyotrophic Lateral Sclerosis Among American Indians and Alaska Natives

Cited by 33 publications

References 26 publications

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis

Dysregulation of MicroRNAs and Target Genes Networks in Peripheral Blood of Patients With Sporadic Amyotrophic Lateral Sclerosis

Association between premorbid body mass index and amyotrophic lateral sclerosis: causal inference through genetic approaches

Encephalitis-Associated Hospitalizations among American Indians and Alaska Natives

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