Dataset Information

Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: the EPIC cohort.

ABSTRACT: The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design.The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were measured. Cox hazard models were fitted to investigate the associations between anthropometric measures and ALS mortality.Two hundred twenty-two ALS deaths (79 men and 143 women) occurred during the follow-up period (mean follow-up = 13 years). There was a statistically significant interaction between categories of body mass index and sex regarding ALS risk (p = 0.009): in men, a significant linear decrease of risk per unit of body mass index was observed (hazard ratio = 0.93, 95% confidence interval 0.86-0.99 per kg/m(2)); among women, the risk was more than 3-fold increased for underweight compared with normal-weight women. Among women, a significant risk reduction increasing the waist/hip ratio was also evident: women in the top quartile had less than half the risk of ALS compared with those in the bottom quartile (hazard ratio = 0.48, 95% confidence interval 0.25-0.93) with a borderline significant p value for trend across quartiles (p = 0.056).Increased prediagnostic body fat is associated with a decreased risk of ALS mortality.

SUBMITTER: Gallo V

PROVIDER: S-EPMC3598455 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: the EPIC cohort.

Gallo Valentina V Wark Petra A PA Jenab Mazda M Pearce Neil N Brayne Carol C Vermeulen Roel R Andersen Peter M PM Hallmans Goran G Kyrozis Andreas A Vanacore Nicola N Vahdaninia Mariam M Grote Verena V Kaaks Rudolf R Mattiello Amalia A Bueno-de-Mesquita H Bas HB Peeters Petra H PH Travis Ruth C RC Petersson Jesper J Hansson Oskar O Arriola Larraitz L Jimenez-Martin Juan-Manuel JM Tjønneland Anne A Halkjær Jytte J Agnoli Claudia C Sacerdote Carlotta C Bonet Catalina C Trichopoulou Antonia A Gavrila Diana D Overvad Kim K Weiderpass Elisabete E Palli Domenico D Quirós J Ramón JR Tumino Rosario R Khaw Kay-Tee KT Wareham Nicholas N Barricante-Gurrea Aurelio A Fedirko Veronika V Ferrari Pietro P Clavel-Chapelon Françoise F Boutron-Ruault Marie-Christine MC Boeing Heiner H Vigl Matthaeus M Middleton Lefkos L Riboli Elio E Vineis Paolo P

Neurology 20130206 9

<h4>Objectives</h4>The aim of this study was to investigate for the first time the association between body fat and risk of amyotrophic lateral sclerosis (ALS) with an appropriate prospective study design.<h4>Methods</h4>The EPIC (European Prospective Investigation into Cancer and Nutrition) study included 518,108 individuals recruited from the general population across 10 Western European countries. At recruitment, information on lifestyle was collected and anthropometric characteristics were m ...[more]

PMID: 23390184

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Project description:ImportanceWhile systemic inflammation has been implicated in the aetiology of selected neurodegenerative disorders, its role in the development of amyotrophic lateral sclerosis (ALS) is untested.ObjectiveTo quantify the relationship of C-reactive protein (CRP), an acute-phase reactant and marker of systemic inflammation, with ALS occurrence.Design setting participantsUK Biobank, a prospective cohort study of 502,649 participants who were aged 37 to 73 years when examined at research centres between 2006 and 2010.ExposureVenous blood was collected at baseline in the full cohort and assayed for CRP. Repeat measurement was made 3-7 years later in a representative subgroup (N=14,514) enabling correction for regression dilution.Main outcomes and measuresALS as ascertained via national hospitalisation and mortality registries. We computed multi-variable hazard ratios with accompanying 95% confidence intervals for log-transformed CRP expressed as standard deviation and tertiles.ResultsIn an analytical sample of 400,884 individuals (218,203 women), a mean follow-up of 12 years gave rise to 231 hospitalisations and 223 deaths ascribed to ALS. After adjustment for covariates which included health behaviours, comorbidity, and socio-economic status, a one standard deviation higher log-CRP was associated with elevated rates of both ALS mortality (hazard ratios; 95% confidence intervals: 1.32; 1.13, 1.53) and hospitalisations (1.20; 1.00, 1.39). There was evidence of dose-response effects across tertiles of CRP for both outcomes (p for trend≤0.05). Correction for regression dilution led to a strengthening of the relationship with CRP for both mortality (1.62; 1.27, 2.08) and hospitalisations (1.37; 1.05, 1.76) ascribed to ALS.Conclusions and relevanceHigher levels of CRP, a blood-based biomarker widely captured in clinical practice, were associated with a higher subsequent risk of ALS.Key pointsQuestion: Is C-reactive protein (CRP), a marker of systemic inflammation widely used in clinical practice, associated with later risk of amyotrophic lateral sclerosis (ALS)?Findings: Following 11 years disease surveillance in 400,884 individuals (218,203 women), after adjustment for covariates and correction for regression dilution, a one standard deviation higher CRP levels were associations with both mortality (hazard ratio; 95% confidence interval: 1.62; 1.27, 2.08) and hospitalisations (1.37; 1.05, 1.76) ascribed to ALS.Meaning: In the present study, CRP has a dose-response relationship with the risk of later ALS.

Project description:ImportanceHeritability describes the proportion of variance in the risk of developing a condition that is explained by genetic factors. Although amyotrophic lateral sclerosis (ALS) is known to have a complex genetic origin, disease heritability remains unclear.ObjectivesTo determine the extent of ALS heritability and assess the association of sex with disease transmission.Design, setting, and participantsA prospective population-based parent-offspring heritability study was conducted from January 1, 2008, to December 31, 2017 to assess ALS heritability, and was the first study to assess heritability in the context of known gene mutations of large effect. A total of 1123 incident cases of ALS, diagnosed according to the El Escorial criteria and recorded on the Irish ALS register, were identified. Ninety-two individuals were excluded (non-Irish parental origin [n = 86] and familial ALS [n = 6]), and 1117 patients were included in the final analysis.Main outcomes and measuresAnnual age-specific and sex-specific standardized ALS incidence and mortality-adjusted lifetime risk were determined. Sex-specific heritability estimates were calculated for the overall study cohort, for those known to carry the C9orf72 (OMIM 614260) variant, and for those with no known genetic risk.ResultsA total of 32 parent-child ALS dyads were identified during the study period. Affected offspring were younger at the onset of disease (mean age, 52.0 years; 95% CI, 48.8-55.3 years) compared with their parents (mean age, 69.6 years; 95% CI, 62.4-76.9 years; P = .008). Lifetime risk of developing ALS in first-degree relatives of individuals with ALS was increased compared with the general population (1.4% [32 of 2234] vs 0.3% [2.6 of 1000]; P < .001). Mean lifetime heritability of ALS for the overall study cohort was 52.3% (95% CI, 42.9%-61.7%) and 36.9% (95% CI, 19.8%-53.9%) for those with no known genetic risk. Heritability estimates were highest in mother-daughter pairings (66.2%; 95% CI, 58.5%-73.9%).Conclusions and relevanceThis population-based study confirms that up to 50% of variance in ALS has a genetic basis, and that the presence of the C9orf72 variant is an important determinant of heritability. First-degree relatives of individuals with ALS without a known genetic basis remain at increased risk of developing ALS compared with the general population. A higher heritability estimate in mother-daughter pairings points to a sex-mediated effect that has been previously unrecognized.

Dataset Information

Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: the EPIC cohort.

Publications

Prediagnostic body fat and risk of death from amyotrophic lateral sclerosis: the EPIC cohort.

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