title: Emerging effects of early environmental factors over genetic background for type 1 diabetes susceptibility: evidence from a Nationwide Italian Twin Study.
abstract: BACKGROUND
  The incidence of type 1 diabetes has been increasing over time.
  
  
  OBJECTIVE
  We estimated the genetic and environmental components of type 1 diabetes susceptibility in a twin cohort of recent-onset cases to explore the sources of changing disease epidemiology.
  
  
  METHODS
  We linked the population-based Italian Twin Registry with 14803 type 1 diabetes records from 36 pediatric diabetes care centers throughout Italy, except Sardinia, and identified 173 diabetic twins. Patients were positive for at least one autoantibody to islet cell, glutamate decarboxylase, tyrosine phosphatase, insulin, or zinc transporter 8 and were insulin dependent since their diagnosis. Zygosity was determined by DNA genotyping or by questionnaire.
  
  
  METHODS
  We estimated proband-wise concordance, cotwin recurrence risk with Kaplan-Meier method, and genetic and environmental proportions of susceptibility variance by structural equation models.
  
  
  RESULTS
  We recruited 104 diabetic twins (53 males) from 88 pairs (34 monozygotic, 54 dizygotic) and one triplet. The mean age at diagnosis was 8.1 yr (range 1.1-20.5 yr), and the median year of diagnosis was 2002. Proband-wise concordances were 45.5 and 16.4% in monozygotic and dizygotic pairs (P = 0.01). Recurrence risks in monozygotic and dizygotic cotwins were 37 and 12% after 10 yr from the proband's diagnosis (P = 0.005). Genetic contribution to type 1 diabetes susceptibility was 40% (95% confidence interval 8-78), and the shared and individual-specific environmental components were 51% (14-77) and 9% (4-19), respectively.
  
  
  CONCLUSIONS
  In addition to the moderate genetic effects on type 1 diabetes susceptibility, our results draw attention to the substantial shared environmental effects, suggesting that exposures in fetal or early postnatal life may contribute to the increasing incidence of the disease.
authors.affiliation: Genetic Epidemiology Unit, National Institute of Health, National Centre of Epidemiology, Surveillance, and Health Promotion, 00161 Rome, Italy. lorenza.nistico@iss.it
authors.forename: Lorenza
authors.initials: L
authors.lastname: Nisticò
authors.forename: Dario
authors.initials: D
authors.lastname: Iafusco
authors.forename: Alfonso
authors.initials: A
authors.lastname: Galderisi
authors.forename: Corrado
authors.initials: C
authors.lastname: Fagnani
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Cotichini
authors.forename: Virgilia
authors.initials: V
authors.lastname: Toccaceli
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Stazi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic