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The Role of Sibling Kinship, Sex, and Age of Ischemic Stroke Onset: The Familial Component

Reporter: Aviva Lev-Ari, PhD, RN

Familial Effects on Ischemic Stroke – The Role of Sibling Kinship, Sex, and Age of Onset

Katherine Kasiman, MSc, Cecilia Lundholm, MSc, Sven Sandin, MSc, Ninoa Malki, MSc, Pär Sparén, PhD and Erik Ingelsson, MD, PhD

Author Affiliations

From the Department of Medical Epidemiology and Biostatistics (K.K., C.L., S.S., N.M., P.S., E.I.), Karolinska Institutet, Stockholm, Sweden; Centre for Molecular Epidemiology (K.K.), Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

Correspondence to Prof Erik Ingelsson, MD, PhD, FAHA, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, Nobels väg 12A, SE-171 77 Stockholm, Sweden. E-mail erik.ingelsson@ki.se

Abstract

Background—Previous studies on familial risk of ischemic stroke have supported genetic influence on the disease incidence. This study aimed to characterize these familial effects in a nationwide population-based study by taking into account sibling relations, sex of siblings, and age of onset, with respect to ischemic stroke incidence.

Methods and Results—Incident ischemic stroke cases identified from the Swedish Hospital Discharge and Cause of Death Registers between 1987 and 2007 were linked to their stroke-free siblings (study participants), forming an exposed sib-pair. Each exposed sib-pair was matched up to 5 unexposed sib-pairs from the Multi-Generation Registry by birth and calendar years. Incident ischemic stroke risk was assessed using hazard estimates obtained from stratified Cox regression analyses. A total of 30 735 exposed and 152 391 unexposed study participants were included in the analyses. The overall risk of incident ischemic stroke when exposed was significantly increased (relative risk, 1.61; 95% confidence interval, 1.48–1.75;P<0.001). Familial risk was higher in full (relative risk, 1.64; 95% confidence interval, 1.50–1.81; P<0.001) than in half (relative risk, 1.41; 95% confidence interval, 1.10–1.82; P=0.007) siblings. Familial risk of early ischemic stroke almost doubled when exposed to early ischemic stroke (relative risk, 1.94; 95% confidence interval, 1.41–2.67; P<0.001).

Conclusions—There was a 60% increased risk for ischemic stroke in individuals having a sibling with prior stroke. The familial effect was even higher for full-sibling relations. Familial effects were observed in both male and female individuals, and no differential effects depending on the sex of either of the siblings were found.

Published online before print March 8, 2012,

doi: 10.1161/ CIRCGENETICS.111.962191

http://circgenetics.ahajournals.org/content/5/2/226.abstract?sid=5201ab39-7f11-4007-b159-2d1e15663cd5