TY - JOUR
T1 - Familial aggregation of congenital hydrocephalus in a nationwide cohort
AU - Munch, Tina Nørgaard
AU - Rostgaard, Klaus
AU - Rasmussen, Marie-Louise Hee
AU - Wohlfahrt, Jan
AU - Melbye, Mads
AU - Juhler, Marianne
PY - 2012/8
Y1 - 2012/8
N2 - The objective of the study was to investigate familial aggregation of primary congenital hydrocephalus in an unselected, nationwide population. Based on the Danish Central Person Register, we identified all children born in Denmark between 1978 and 2008 and their family members (up to third-degree relatives). Information on primary congenital hydrocephalus was obtained from the National Patient Discharge Register. Using binomial log-linear regression, we estimated recurrence risk ratios of congenital hydrocephalus. An alternative log-linear regression model was applied to quantify the genetic effect and the maternal effect. Of 1 928 683 live-born children, 2194 had a diagnosis of idiopathic congenital hydrocephalus (1.1/1000). Of those, 75 (3.4%) had at least one other family member with primary congenital hydrocephalus. Significantly increased recurrence risk ratios of primary congenital hydrocephalus were observed for same-sex twins, first- and second-degree relatives as follows: 34.8 (95% confidence interval: 16.4-74.0), 6.2 (95% confidence interval 4.3-8.9) and 2.2 (95% confidence interval 1.6-3.1), respectively. Recurrence risk ratio for third-degree relatives was 1.5 (95% confidence interval 0.8-2.7). A maternal component was supported by the facts that recurrence risk ratios for opposite-sex twins (37.3, 95% confidence interval 11.9-116.7) were significantly higher than other first-degree relatives and that recurrence risk ratios for maternal half-siblings (8.4, 95% confidence interval 3.7-18.7) were significantly higher than for paternal half-siblings (3.0, 95% confidence interval 0.8-12.2). This population-based study found strong evidence of familial aggregation of primary congenital hydrocephalus, which supports the existence of a genetic component to the aetiology. In addition, the pattern of association suggests that a strong maternal component contributes to the familial aggregation.
AB - The objective of the study was to investigate familial aggregation of primary congenital hydrocephalus in an unselected, nationwide population. Based on the Danish Central Person Register, we identified all children born in Denmark between 1978 and 2008 and their family members (up to third-degree relatives). Information on primary congenital hydrocephalus was obtained from the National Patient Discharge Register. Using binomial log-linear regression, we estimated recurrence risk ratios of congenital hydrocephalus. An alternative log-linear regression model was applied to quantify the genetic effect and the maternal effect. Of 1 928 683 live-born children, 2194 had a diagnosis of idiopathic congenital hydrocephalus (1.1/1000). Of those, 75 (3.4%) had at least one other family member with primary congenital hydrocephalus. Significantly increased recurrence risk ratios of primary congenital hydrocephalus were observed for same-sex twins, first- and second-degree relatives as follows: 34.8 (95% confidence interval: 16.4-74.0), 6.2 (95% confidence interval 4.3-8.9) and 2.2 (95% confidence interval 1.6-3.1), respectively. Recurrence risk ratio for third-degree relatives was 1.5 (95% confidence interval 0.8-2.7). A maternal component was supported by the facts that recurrence risk ratios for opposite-sex twins (37.3, 95% confidence interval 11.9-116.7) were significantly higher than other first-degree relatives and that recurrence risk ratios for maternal half-siblings (8.4, 95% confidence interval 3.7-18.7) were significantly higher than for paternal half-siblings (3.0, 95% confidence interval 0.8-12.2). This population-based study found strong evidence of familial aggregation of primary congenital hydrocephalus, which supports the existence of a genetic component to the aetiology. In addition, the pattern of association suggests that a strong maternal component contributes to the familial aggregation.
U2 - 10.1093/brain/aws158
DO - 10.1093/brain/aws158
M3 - Journal article
C2 - 22763745
SN - 0006-8950
VL - 135
SP - 2409
EP - 2415
JO - Brain
JF - Brain
IS - Pt 8
ER -