Differences in Common Genetic Predisposition to Ischemic Stroke by Age and Sex

Traylor, M; Rutten-Jacobs, LCA; Holliday, EG; Malik, R; Sudlow, C; Rothwell, PM; Maguire, JM; Koblar, SA; Bevan, S; Boncoraglio, G; Dichgans, M; Levi, C; Lewis, CM; Markus, HS

Differences in Common Genetic Predisposition to Ischemic Stroke by Age and Sex

Traylor, M Rutten-Jacobs, LCA Holliday, EG Malik, R Sudlow, C Rothwell, PM Maguire, JM

Koblar, SA Bevan, S Boncoraglio, G Dichgans, M Levi, C Lewis, CM Markus, HS

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Publication Type:: Journal Article
Citation:: Stroke, 2015, 46 (11), pp. 3042 - 3047
Issue Date:: 2015-11-01

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Field	Value	Language
dc.contributor.author	Traylor, M	en_US
dc.contributor.author	Rutten-Jacobs, LCA	en_US
dc.contributor.author	Holliday, EG	en_US
dc.contributor.author	Malik, R	en_US
dc.contributor.author	Sudlow, C	en_US
dc.contributor.author	Rothwell, PM	en_US
dc.contributor.author	Maguire, JM https://orcid.org/0000-0001-5722-8311	en_US
dc.contributor.author	Koblar, SA	en_US
dc.contributor.author	Bevan, S	en_US
dc.contributor.author	Boncoraglio, G	en_US
dc.contributor.author	Dichgans, M	en_US
dc.contributor.author	Levi, C	en_US
dc.contributor.author	Lewis, CM	en_US
dc.contributor.author	Markus, HS	en_US
dc.date.available	2015-08-04	en_US
dc.date.issued	2015-11-01	en_US
dc.identifier.citation	Stroke, 2015, 46 (11), pp. 3042 - 3047	en_US
dc.identifier.issn	0039-2499	en_US
dc.identifier.uri	http://hdl.handle.net/10453/119325
dc.description.abstract	© 2015 American Heart Association, Inc. Background and Purpose-Evidence from epidemiological studies points to differences in factors predisposing to stroke by age and sex. Whether these arise because of different genetic influences remained untested. Here, we use data from 4 genome-wide association data sets to study the relationship between genetic influence on stroke with both age and sex. Methods-Using genomic-relatedness-matrix restricted maximum likelihood methods, we performed 4 analyses: (1) we calculated the genetic correlation between groups divided by age and (2) by sex, (3) we calculated the heritability of age-at-stroke-onset, and (4) we evaluated the evidence that heritability of stroke is greater in women than in men. Results-We found that genetic factors influence age at stroke onset (h2 [SE]=18.0 [6.8]; P=0.0038), with a trend toward a stronger influence in women (women: h2 [SE]=21.6 [3.5]; Men: h2 [SE]=13.9 [2.8]). Although a moderate proportion of genetic factors was shared between sexes (rG [SE]=0.68 [0.16]) and between younger and older cases (rG [SE]=0.70 [0.17]), there was evidence to suggest that there are genetic susceptibility factors that are specific to sex (P=0.037) and to younger or older groups (P=0.056), particularly for women (P=0.0068). Finally, we found a trend toward higher heritability of stroke in women although this was not significantly greater than in men (P=0.084). Conclusions-Our results indicate that there are genetic factors that are either unique to or have a different effect between younger and older age groups and between women and men. Performing large, well-powered genome-wide association study analyses in these groups is likely to uncover further associations.	en_US
dc.relation.ispartof	Stroke	en_US
dc.relation.isbasedon	10.1161/STROKEAHA.115.009816	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Brain Ischemia	en_US
dc.subject.mesh	Genetic Predisposition to Disease	en_US
dc.subject.mesh	Cohort Studies	en_US
dc.subject.mesh	Aging	en_US
dc.subject.mesh	Sex Characteristics	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Aged	en_US
dc.subject.mesh	Aged, 80 and over	en_US
dc.subject.mesh	Middle Aged	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Stroke	en_US
dc.subject.mesh	Genome-Wide Association Study	en_US
dc.title	Differences in Common Genetic Predisposition to Ischemic Stroke by Age and Sex	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.citation.volume	46	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	1109 Neurosciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
utslib.copyright.status	open_access
pubs.issue	11	en_US
pubs.publication-status	Published	en_US
pubs.volume	46	en_US

Abstract:

© 2015 American Heart Association, Inc. Background and Purpose-Evidence from epidemiological studies points to differences in factors predisposing to stroke by age and sex. Whether these arise because of different genetic influences remained untested. Here, we use data from 4 genome-wide association data sets to study the relationship between genetic influence on stroke with both age and sex. Methods-Using genomic-relatedness-matrix restricted maximum likelihood methods, we performed 4 analyses: (1) we calculated the genetic correlation between groups divided by age and (2) by sex, (3) we calculated the heritability of age-at-stroke-onset, and (4) we evaluated the evidence that heritability of stroke is greater in women than in men. Results-We found that genetic factors influence age at stroke onset (h2 [SE]=18.0 [6.8]; P=0.0038), with a trend toward a stronger influence in women (women: h2 [SE]=21.6 [3.5]; Men: h2 [SE]=13.9 [2.8]). Although a moderate proportion of genetic factors was shared between sexes (rG [SE]=0.68 [0.16]) and between younger and older cases (rG [SE]=0.70 [0.17]), there was evidence to suggest that there are genetic susceptibility factors that are specific to sex (P=0.037) and to younger or older groups (P=0.056), particularly for women (P=0.0068). Finally, we found a trend toward higher heritability of stroke in women although this was not significantly greater than in men (P=0.084). Conclusions-Our results indicate that there are genetic factors that are either unique to or have a different effect between younger and older age groups and between women and men. Performing large, well-powered genome-wide association study analyses in these groups is likely to uncover further associations.

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http://hdl.handle.net/10453/119325