The journal of headache and pain
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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. 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. ⋯ Polygenic 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.
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Pituitary adenylate-cyclase-activating polypeptide (PACAP) is a 27- or 38-amino acid neuropeptide, which belongs to the vasoactive intestinal polypeptide (VIP)/glucagon/secretin family. PACAP shows particularly high homology (~ 68%) to VIP. ⋯ These receptors have high homology to each other, and their high homology is utilized for these discoveries. This review provides mainly an overview of the history of the discovery of PACAP and its three receptors.