BACKGROUND: Previous familial segregation studies supported that developmental dysplasia of the hip (DDH) is a multifactorial genetic disease. However, the exact extent of genetic effects has not been fully evaluated, especially in Asian population. The aim of this study is to estimate the sibling recurrent risk and heritability of DDH in a large Chinese cohort. MATERIALS AND METHODS: Four hundred and twenty-nine DDH probands and 534 matched normal controls were recruited from a screening programme for DDH, including 628 siblings in families of probands and 889 siblings in those of controls, respectively. The detailed information of family history was obtained, and the prevalence of DDH among siblings of probands, as well as controls, was determined. The sibling recurrent risk and heritability was estimated using classical liability threshold model. RESULTS: Eighty-seven siblings (13.85%) in families of proband and 14 siblings (1.57%) in normal control families were diagnosed as DDH. The recurrent risk in siblings of probands was at least tenfolds that in siblings of controls. Compared with the normal controls, the sibling recurrent risk was about 12-fold increase in male sib, and 9-fold increase in female sib. Overall, a high heritability of 83.59 ± 4.90% (h(2) ± SE) was observed. When stratified by genders, it was even higher for female siblings (91.02 ± 7.25%). CONCLUSION: This study for the first time exhibits a high sibling recurrent risk and heritability for DDH in Asian population. It also shows there is a high probability to identify the underlying predisposition genes in future genetic study.
BACKGROUND: Previous familial segregation studies supported that developmental dysplasia of the hip (DDH) is a multifactorial genetic disease. However, the exact extent of genetic effects has not been fully evaluated, especially in Asian population. The aim of this study is to estimate the sibling recurrent risk and heritability of DDH in a large Chinese cohort. MATERIALS AND METHODS: Four hundred and twenty-nine DDH probands and 534 matched normal controls were recruited from a screening programme for DDH, including 628 siblings in families of probands and 889 siblings in those of controls, respectively. The detailed information of family history was obtained, and the prevalence of DDH among siblings of probands, as well as controls, was determined. The sibling recurrent risk and heritability was estimated using classical liability threshold model. RESULTS: Eighty-seven siblings (13.85%) in families of proband and 14 siblings (1.57%) in normal control families were diagnosed as DDH. The recurrent risk in siblings of probands was at least tenfolds that in siblings of controls. Compared with the normal controls, the sibling recurrent risk was about 12-fold increase in male sib, and 9-fold increase in female sib. Overall, a high heritability of 83.59 ± 4.90% (h(2) ± SE) was observed. When stratified by genders, it was even higher for female siblings (91.02 ± 7.25%). CONCLUSION: This study for the first time exhibits a high sibling recurrent risk and heritability for DDH in Asian population. It also shows there is a high probability to identify the underlying predisposition genes in future genetic study.
Authors: Konstantinos Hatzikotoulas; Andreas Roposch; Karan M Shah; Matthew J Clark; Selina Bratherton; Vasanti Limbani; Julia Steinberg; Eleni Zengini; Kaltuun Warsame; Madhushika Ratnayake; Maria Tselepi; Jeremy Schwartzentruber; John Loughlin; Deborah M Eastwood; Eleftheria Zeggini; J Mark Wilkinson Journal: Commun Biol Date: 2018-05-31