Sex differences in heritability of ischemic stroke: a systematic review and meta-analysis.
OBJECTIVE
Using data from Oxfordshire, UK, we recently showed that women are more likely than men to have a family history of stroke in female versus male first degree relatives. To test the generalizability of this finding, we did a comprehensive systematic review of all available published and unpublished data.


METHODS
Studies were included in the present review if they reported the frequency of family history of stroke in relation to sex of parent or proband. Where necessary, we contacted authors of studies to obtain unpublished data. Data from the Oxford Vascular Study (OXVASC) and 3 other Oxford cohorts (1925 patients) were secondarily pooled with the data from other studies.


RESULTS
We obtained data from 18 studies (7941 patients), including unpublished data from 7 studies. Female probands were slightly more likely to have a parental history of stroke than male probands (pooled OR=1.15; 95% CI: 1.03 to 1.29; P((sig))=0.028; P((het))=0.45). Maternal history of stroke was more common than paternal history (pooled OR=1.25; 1.15 to 1.37; P((sig))<0.00001; P((het))=0.12). However, the maternal excess was only present in female probands (pooled OR=1.47; 1.27 to 1.70; P((sig))<0.00001; P((het))=0.11). In contrast, male probands were no more likely to have maternal than paternal history of stroke (pooled OR=1.02; 0.88 to 1.17, P((sig))=0.43; P((het))=0.09).


CONCLUSIONS
Women with stroke are more likely than men to have a parental history of stroke, which is accounted for by an excess maternal history of stroke. This finding could be explained by sex-specific genetic, epigenetic, or nongenetic mechanisms.
Touzé
Emmanuel
E
Stroke Prevention Research Unit, University Department of Clinical Neurology, Radcliffe Infirmary, Oxford OX2 6HE, UK.
Rothwell
Peter M
PM
D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D012307:Risk Factors; D012727:Sex Characteristics; D020521:Stroke / Q000235:genetics*; D006113:United Kingdom