title: Twin studies in multiple sclerosis: A meta-estimation of heritability and environmentality.
abstract: BACKGROUND
  Most twin studies of multiple sclerosis (MS) are inconclusive regarding the impact of genes and environment on disease susceptibility. In particular, high uncertainty exists about whether shared environmental factors are aetiologically relevant.
  
  
  OBJECTIVE
  To disentangle, with a reasonable degree of confidence, the relative contributions of heritability and of shared and unique environmental components of MS susceptibility.
  
  
  METHODS
  We performed a meta-analysis of previous twin studies. After a MEDLINE search, we selected eight twin studies in France, UK, Canada, Denmark, North America, Italy, Finland and Sweden. We conducted a biometric multi-group analysis under the liability-threshold model, by taking account of the study-specific ascertainment strategies and the population-specific prevalence rates of MS.
  
  
  RESULTS
  The meta-analytic estimates of tetrachoric correlations were 0.71 (95% confidence interval (CI): 0.67-0.74) in monozygotic pairs and 0.46 (95% CI: 0.41-0.50) in dizygotic pairs. The biometric multi-group model provided meta-analytic estimates of 0.50 (95% CI: 0.39-0.61) for heritability, 0.21 (95% CI: 0.11-0.30) for shared environmental component and 0.29 (95% CI: 0.26-0.33) for unique environmental component.
  
  
  CONCLUSIONS
  Our results support the continuing efforts to identify unknown genetic factors that fill the gap of 'missing heritability'; moreover, a 'missing environmentality' deserves future investigations into the role of non-heritable components that act as both shared and individual-specific exposures.
authors.affiliation: National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy corrado.fagnani@iss.it.
authors.forename: Corrado
authors.initials: C
authors.lastname: Fagnani
authors.affiliation: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Neale
authors.affiliation: National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Nisticò
authors.affiliation: National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Stazi
authors.affiliation: Centre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), 'Sapienza' University of Rome, Italy.
authors.forename: Vito A
authors.initials: VA
authors.lastname: Ricigliano
authors.affiliation: Centre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), 'Sapienza' University of Rome, Italy.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Buscarinu
authors.affiliation: Centre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), 'Sapienza' University of Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Salvetti
authors.affiliation: Centre for Experimental Neurological Therapies (CENTERS), Neurology and Department of Neurosciences, Mental Health and Sensory Organs (NESMOS), 'Sapienza' University of Rome, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ristori
mesh_terms: D004777:Environment; D020022:Genetic Predisposition to Disease; D006801:Humans; D009103:Multiple Sclerosis / Q000209:etiology* / Q000235:genetics*; D018433:Twin Studies as Topic
keywords: Multiple sclerosis; aetiology; environment; genetic predisposition to disease; meta-analysis; twin study