January 03, 2020
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Genomic risk score may predict ischemic stroke

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A genomic risk score developed with a meta-scoring approach may predict the risk for ischemic stroke, according to a study published in Nature Communications.

“The sequencing of the human genome has revealed many insights,” Michael Inouye, PhD, head of the systems genomics lab at Baker Heart and Diabetes Institute in Melbourne, Australia, said in a press release. “For common diseases such as stroke, it is clear that genetics is not destiny; however, each person does have their own innate risk for any particular disease. The challenge is now how we best incorporate this risk information into clinical practice so that the public can live healthier and longer.”

Gad Abraham , PhD, group leader of systems genomics at Baker Heart and Diabetes Institute, and colleagues developed a genomic risk score to predict ischemic stroke using a meta-scoring approach. The risk score was then evaluated in a validation group of 395,393 patients (mean age, 57 years; 46% men) from the UK Biobank who had an ischemic stroke event by age 75 years.

The genomic risk score was linked to ischemic stroke with a HF of 1.26 per standard deviation (95% CI, 1.22-1.31). This association was stronger compared with any individual genetic risk score that made up the meta-scoring approach risk score (HR = 1.18; 95% CI, 1.15-1.22). It was also twice as effective as the 90-SNP ischemic stroke score (HR = 1.13; 95% CI, 1.1-1.17).

Patients who comprised the top 0.25% of the population had a threefold increased risk for ischemic stroke compared with patients who were in the 45% to 55% of the population (HR = 3; 95% CI, 1.96-4.59).

The genomic risk score developed with a meta-scoring approach (incident ischemic stroke HR = 1.25 per standard deviation) had similar HRs to current smoking (incident ischemic stroke HR = 1.25 per standard deviation) and systolic BP (incident ischemic stroke HR = 1.28 per standard deviation). This developed score had a greater C-index compared with a family history of stroke (C = 0.558; 95% CI, 0.544-0.572).

Using the risk score, reductions in modifiable risk factors including systolic BP, smoking and BMI to match guideline targets may reduce the risk for ischemic stroke to 2.8% in men (95% CI, 1.7-3.9) and to 1.7% in women (95% CI, 1-2.4).

“Taken together, despite challenges in phenotypic heterogeneity and corresponding genome-wide association study power, our study presents the most powerful ischemic stroke genomic risk score to date and assesses its potential for risk stratification in the context of established risk factors and clinical guidelines,” Abraham and colleagues wrote. “It lays the groundwork for larger genome-wide association study of stroke and its multiple subtypes as well as analyses which leverage the totality of information available for stroke genomic risk prediction.” – by Darlene Dobkowski

Disclosures: Inouye and Abraham report no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.