Chang-Fu Kuo1,2, Yu-Sheng Lin3,4, Shang-Hung Chang5, I-Jun Chou6, Shue-Fen Luo2, Lai-Chu See7, Kuang-Hui Yu2, Lu-Shuang Huang2, Pao-Hsien Chu3,5,8. 1. Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham. 2. Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital. 3. Healthcare Center, Chang Gung Memorial Hospital. 4. Division of Internal Medicine, Chang Gung Memorial Hospital. 5. Division of Cardiology, Chang Gung Memorial Hospital. 6. Division of Pediatric Neurology, Chang Gung Memorial Hospital. 7. Department of Public Health, College of Medicine and Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University. 8. Heart Failure Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine.
Abstract
BACKGROUND: Congenital heart defects (CHD) are known to cluster within families, but existing evidence varies for the estimates of familial relative risk (RR). We aimed to examine familial aggregation and heritability of CHD in the general population of Taiwan.Methods and Results: We conducted a population-based family study using the Taiwan National Health Insurance (NHI) research database. Individuals with affected first-degree (n=295,636) or second-degree (n=73,985) relatives were identified from all NHI beneficiaries (n=23,422,955) registered in 2012. Diagnoses of CHD for all study subjects were ascertained between January 1, 1996 and December 31, 2012. Having a twin, a first-degree relative and an affected second-degree relative were associated with an adjusted RR of 12.03 (11.59-12.49), 4.91 (4.85-4.97) and 1.21 (1.14-1.28) for CHD, respectively. Individuals with 1 affected first-degree relative had a RR of 4.78 (4.72-4.84), and those with ≥2 had an RR of 7.10 (6.77-7.45) for CHD. The estimated accountability for phenotypic variance of CHD was 37.3% for familial transmission and 62.8% for non-shared environmental factors. CONCLUSIONS: Our results indicated that CHD tend to cluster within families, and approximately one-third of phenotypic variance was explained by familial factors.
BACKGROUND:Congenital heart defects (CHD) are known to cluster within families, but existing evidence varies for the estimates of familial relative risk (RR). We aimed to examine familial aggregation and heritability of CHD in the general population of Taiwan.Methods and Results: We conducted a population-based family study using the Taiwan National Health Insurance (NHI) research database. Individuals with affected first-degree (n=295,636) or second-degree (n=73,985) relatives were identified from all NHI beneficiaries (n=23,422,955) registered in 2012. Diagnoses of CHD for all study subjects were ascertained between January 1, 1996 and December 31, 2012. Having a twin, a first-degree relative and an affected second-degree relative were associated with an adjusted RR of 12.03 (11.59-12.49), 4.91 (4.85-4.97) and 1.21 (1.14-1.28) for CHD, respectively. Individuals with 1 affected first-degree relative had a RR of 4.78 (4.72-4.84), and those with ≥2 had an RR of 7.10 (6.77-7.45) for CHD. The estimated accountability for phenotypic variance of CHD was 37.3% for familial transmission and 62.8% for non-shared environmental factors. CONCLUSIONS: Our results indicated that CHD tend to cluster within families, and approximately one-third of phenotypic variance was explained by familial factors.