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Numerous biological mechanisms contribute to outcome after stroke, including brain injury, inflammation, and repair mechanisms. Clinical genetic studies have the potential to discover biological mechanisms affecting stroke recovery in humans and identify intervention targets. Large sample sizes are needed to detect commonly occurring genetic variations related to stroke brain injury and recovery. However, this usually requires combining data from multiple studies where consistent terminology, methodology, and data collection timelines are essential. Our group of expert stroke and rehabilitation clinicians and researchers with knowledge in genetics of stroke recovery here present recommendations for harmonizing phenotype data with focus on measures suitable for multicenter genetic studies of ischemic stroke brain injury and recovery. Our recommendations have been endorsed by the International Stroke Genetics Consortium.

© The Author(s) 2019. Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may therefore have therapeutic benefit for ischaemic stroke. This systematic review assessed whether upregulating angiopoietin-1 improved outcomes in rodent models of ischaemic stroke. Random-effects models quantified the effect of angiopoietin-1 upregulation on stroke severity in terms of the size of cerebral infarction and the extent of blood–brain barrier permeability. Eleven studies utilising rat and mouse models of ischaemic stroke fulfilled the inclusion criteria. Meta-analyses demonstrated that angiopoietin-1 upregulation significantly reduced cerebral infarction size (standardised mean difference: –3.02; 95% confidence intervals: –4.41, –1.63; p < 0.001; n = 171 animals) and improved blood–brain barrier integrity (standardized mean difference: –2.02; 95% confidence intervals: –3.27, –0.77; p = 0.002; n = 129 animals). Subgroup analyses demonstrated that angiopoietin-1 upregulation improved outcomes in models of transient, not permanent cerebral ischaemia. Six studies assessed the effect of angiopoietin-1 upregulation on neurological function; however, inter-study heterogeneity prevented meta-analysis. In conclusion, published rodent data suggest that angiopoietin-1 upregulation improves outcome following temporary cerebral ischaemia by reducing cerebral infarction size and improving blood–brain barrier integrity. Additional research is required to examine the effect of angiopoietin-1 upregulation on neurological function during stroke recovery and investigate the benefit and risks in patients.

Background and Purpose- Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Methods- Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical power calculation, inverse-variance weighted MR was performed to pool estimates across different instruments. The Cochran Q heterogeneity test, weighted median MR, and MR pleiotropy residual sum and outlier were used to explore possible bias relating to inclusion of pleiotropic variants. Results- There was no MR evidence for an effect of genetically determined risk of depression on ischemic stroke risk. Although suffering low statistical power, the main inverse-variance weighted MR analysis was suggestive of a detrimental effect of genetically determined risk of depression on functional outcome after ischemic stroke (odds ratio of poor outcome [modified Rankin Scale, ≥3] per 1-SD increase in genetically determined risk of depression, 1.81; 95% CI, 0.98-3.35; P=0.06). There was no evidence of heterogeneity between MR estimates produced by different instruments (Q P=0.26). Comparable MR estimates were obtained with weighted median MR (odds ratio, 2.57; 95% CI, 1.05-6.25; P=0.04) and MR pleiotropy residual sum and outlier (odds ratio, 1.81; 95% CI, 0.95-3.46; P=0.08). Conclusions- We found no MR evidence of genetically determined risk of depression affecting ischemic stroke risk but did find consistent MR evidence suggestive of a possible effect on functional outcome after ischemic stroke. Given the widespread prevalence of depression-related morbidity, these findings could have implications for prognostication and personalized rehabilitation after stroke.

Health services are central to the provision of services for those affected by HIV including, prevention, health promotion and treatment. Access to health services for gay men is significant in increasing their knowledge associated with issues relevant to HIV so that they can better protect and care for themselves. Aim: This ethnographic study sought to clarify and further understand the experience of Bangkok’s gay men and their access to health services relevant to HIV issues. Methods: The data collection was conducted between May and August, 2014. 45 to 60 minutes Face to face interview and digital audio recording were utilised for the data collection processes. Semi structured in-depth interviews undertaken at the Thai Red Cross Research Centre, Bangkok. All interview transcripts were translated from Thai to English. The NVivo program version 10 was utilised to organise the data coding and theming. Result: This study identified that there are few specific clinics for gay men with HIV in Thailand. Additionally, information associated with HIV and other related concerns are required to be more accurate and specific to men living with HIV. Many chaay rak chaay face difficulties accessing services, including a lack of information, privacy concerns and inadequate provision of services. Conclusion: the specific clinic and information relevant HIV issues need to be more readily available and widely circulated. Moreover, health care services should be aware of the privacy issues and personal confidentially issues. Such approaches toward providing services for gay me in Bangkok may assist in eliminating some of the many barriers faced by gay men when accessing health services in the city.

This qualitative study sought to explore perception of Bangkok’s chaay rak chaay (MSM, men having sex with men) regarding sexuality and HIV infection. Thirty-one chaay rak chaay participants who used services at the Niranam Clinic, supported by The Thai Red Cross, took part in in-depth interviews between May and August, 2014. The findings indicate that most participants did not believe that true love exists in gay life and this was linked to many chaay rak chaay choosing to engage in multiple sexual partners. Participants also indicated that sex is a basis of life and gay men cannot live without sex. In addition, the participants reflected that although they may live with HIV, one can still lead a normal life and that this relied on the degree of social acceptance. However, fear of HIV infection can motivate chaay rak chaay to be more aware of HIV prevention and safe sex behaviours. The findings from this study suggests that both government and non-government organisations should continuously promote a social acceptance of HIV infected groups. In addition, the findings indicated that the impacts of HIV infection needed to be promoted through media sites for the purpose of modifying chaay rak chaay’s perceptions and behaviours around HIV prevention.

Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 × 10-8) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 × 10-4; discovery and replication combined OR = 1.21, P = 4.7 × 10-8). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke. © 2012 Nature America, Inc. All rights reserved.

© 2015 European Academy of Neurology. Background and purpose: Although the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples. Methods: This analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age < 55 years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age ≥ 55 years). Results: Heritabilities for young-onset stroke and old-onset stroke were estimated at 42% (±8%, P < 0.001) and 34% (±10%, P < 0.001), respectively. Conclusions: Our data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.

© 2013 Springer-Verlag London. This chapter describes the strategy of association studies that can be used to characterize the genetics of stroke. It explains advantages and disadvantages of the method and discusses current evidence of the genes that have been associated with stroke.