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The first large population based twin study of coeliac disease
  1. L Greco1,
  2. R Romino1,
  3. I Coto1,
  4. N Di Cosmo1,
  5. S Percopo1,
  6. M Maglio1,
  7. F Paparo1,
  8. V Gasperi1,
  9. M G Limongelli1,
  10. R Cotichini2,
  11. C D'Agate3,
  12. N Tinto4,
  13. L Sacchetti4,
  14. R Tosi5,
  15. M A Stazi2
  1. 1Department of Paediatrics, University of Naples Federico II, Naples, Italy and European Laboratory of Food Induced Disease (ELFID), Naples, Italy
  2. 2Istituto Superiore di Sanità, Rome, Italy
  3. 3Italian Coeliac Society, Southern Italy Regions, Italy
  4. 4Department of Biochemistry and Medical Biotechnologies, University of Naples Federico II, Naples, Italy
  5. 5Cellular Biology Institute, CNR, Rome, Italy
  1. Correspondence to:
    Professor L Greco, Università di Napoli Federico II, Dipartimento di Pediatria, Edificio 11, Via S Pansini 5, 80131 Napoli, Italy;


Background and aims: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study.

Methods: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules.

Results: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1–134), independent of the DQ at risk genotype.

Conclusion: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region.

  • coeliac disease
  • twins
  • HLA typing
  • CD, coeliac disease
  • MZ, monozygotic, DZ, dizygotic
  • AIC, Associazione Italiana Celiachia
  • Cc, concordance rate, Pr, pairwise concordance rate
  • EMA, antiendomysial antibody
  • anti-tTG, antihuman-tissue transglutaminase, OR, odds ratio. ELISA, enzyme linked immunosorbent assay
  • IBS, identity by state

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