Clinical Epidemiology (Oct 2018)
Familial aggregation and heritability of type 1 diabetes mellitus and coaggregation of chronic diseases in affected families
Abstract
Chang-Fu Kuo,1,2,* I-Jun Chou,3,4,* Matthew J Grainge,5 Shue-Fen Luo,2 Lai-Chu See,2,6,7 Kuang-Hui Yu,2 Weiya Zhang,1 Michael Doherty,1 Ana M Valdes1 1Division or Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK; 2Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK; 4Division of Paediatric Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; 5Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK; 6Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University, Taoyuan, Taiwan; 7Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan *These authors contributed equally to this work Purpose: To estimate the extent of familial aggregation of type 1 diabetes (T1D) and coaggregation of related chronic diseases and assess the relative contribution of environmental and genetic factors on the risks.Patients and methods: This population-based study used the Taiwan National Health Insurance database to reconstruct family structure and identify people with T1D and other chronic diseases between 1999 and 2015. Relative risks (RRs) for T1D and other chronic diseases and heritability of T1D were estimated. Heritability was estimated using the polygenic liability model.Results: Validation of family structure found the positive predictive value to be 98.7% for maternal links and 98.6% for paternal links. Having an affected twin, first-degree relative, or spouse was associated with an adjusted RR (95% CI) of 553.66 (427.59–716.89), 32.49 (28.66–36.84), and 2.17 (0.31–15.40) for T1D, respectively. Based on the polygenic liability model, heritability, shared and non-shared contributions to T1D, and variances were 66.50%, 10.86%, and 22.64%, respectively. A family history of T1D was associated with an RR (95% CI) of 1.51 (1.20–1.89) for rheumatoid arthritis, 1.66 (1.21–2.26) for Sjögren’s syndrome, 1.48 (1.09–2.01) for systemic lupus erythematosus, 1.24 (1.14–1.35) for simple goiter, 1.16 (1.04–1.31) for non-toxic nodular goiter, 1.61 (1.49–1.74) for thyrotoxicosis, 1.78 (1.57–2.01) for acquired hypothyroidism, 1.66 (1.40–1.98) for thyroiditis, and 1.15 (0.97–1.37) for epilepsy.Conclusion: These data highlight the importance of the genetic contribution to T1D and confirm the coaggregation of autoimmune and metabolic diseases with T1D. Keywords: type 1 diabetes mellitus, familial aggregation, co-aggregation, autoimmune diseases, endocrine diseases
