Abstract
BackgroundThe latest Genome-Wide Association Study identified 38 genetic variants associated with migraine. In this type of studies the significance level is very difficult to achieve (5 × 10− 8) due to multiple testing. Thus, the identified variants only explain a small fraction of the genetic risk. It is expected that hundreds of thousands of variants also confer an increased risk but do not reach significance levels. One way to capture this information is by constructing a Polygenic Risk Score. Polygenic Risk Score has been widely used with success in genetics studies within neuropsychiatric disorders. The use of polygenic scores is highly relevant as data from a large migraine Genome-Wide Association Study are now available, which will form an excellent basis for Polygenic Risk Score in migraine studies.ResultsPolygenic Risk Score has been used in studies of neuropsychiatric disorders to assess prediction of disease status in case-control studies, shared genetic correlation between co-morbid diseases, and shared genetic correlation between a disease and specific endophenotypes.ConclusionPolygenic Risk Score provides an opportunity to investigate the shared genetic risk between known and previously unestablished co-morbidities in migraine research, and may lead to better and personalized treatment of migraine if used as a clinical assistant when identifying responders to specific drugs. Polygenic Risk Score can be used to analyze the genetic relationship between different headache types and migraine endophenotypes. Finally, Polygenic Risk Score can be used to assess pharmacogenetic effects, and perhaps help to predict efficacy of the Calcitonin Gene-Related Peptide monoclonal antibodies that soon become available as migraine treatment.KeywordsMigraine genetics; Genome-Wide Association Studies; Polygenic Risk Score; pleiotropy; endophenotype.
Highlights
Migraine is a prevalent and disabling disease [1] with an incompletely understood etiopathology
The hereditary component of migraine, i.e. the proportion of individual differences explained by genetic variation in migraine, is estimated to be between 38 and 53% and is likely to arise from the combined effect of many common risk variants each with small effect sizes, characterizing migraine as a common complex, polygenic disease [2,3,4]
There was no polygenic association between suicide attempt and suicidal ideation, suggesting that suicide attempts and suicidal ideation are not part of the same spectrum, the tendency to act on suicidal thoughts may have another proponent than suicidal ideation
Summary
Migraine is a prevalent and disabling disease [1] with an incompletely understood etiopathology. The hereditary component of migraine, i.e. the proportion of individual differences explained by genetic variation in migraine, is estimated to be between 38 and 53% and is likely to arise from the combined effect of many common risk variants each with small effect sizes, characterizing migraine as a common complex, polygenic disease [2,3,4]. We use examples from neuropsychiatric disorders as they are common brain disorders, and PRS has been widely used with great success within this field. The latest Genome-Wide Association Study identified 38 genetic variants associated with migraine. In this type of studies the significance level is very difficult to achieve (5 × 10− 8) due to multiple testing. The identified variants only explain a small fraction of the genetic risk. Polygenic Risk Score has been widely used with success in genetics studies within neuropsychiatric disorders. The use of polygenic scores is highly relevant as data from a large migraine GenomeWide Association Study are available, which will form an excellent basis for Polygenic Risk Score in migraine studies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
