{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:52:46Z","timestamp":1761709966703,"version":"build-2065373602"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education in Saudi Arabia","award":["IFP-2020-46"],"award-info":[{"award-number":["IFP-2020-46"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Migraine, as the seventh most disabling neurological disease with 26.9% prevalence in Saudi females, lacks studies on identifying associated genes and pathways with migraines in the Arab population. This case control study aims to identify the migraine-associated novel genes and risk variants. More than 1900 Arab ancestry young female college students were screened: 103 fulfilled the ICHD-3 criteria for migraine and 20 cases confirmed in the neurology clinic were included for the study with age-matched healthy controls. DNA from blood samples were subjected to paired-end whole-exome sequencing. After quality control, 3365343 missense, frameshift, missense splice region variants and insertion\u2013deletion (indels) polymorphisms were tested for association with migraine. Significant variants were validated using Sanger sequencing. A total of 17 (p-value 9.091 \u00d7 10\u221205) functional variants in 12 genes (RETNLB, SCAI, ADH4, ESPL1, CPT2, FLG, PPP4R1, SERPINB5, ZNF66, ETAA1, EXO1 and CPA6) were associated with higher migraine risk, including a stop-gained frameshift (-13-14*SX) variant in the gene RETNLB (rs5851607; p-value 3.446 \u00d7 10\u221206). Gene analysis revealed that half of the significant novel migraine risk genes were expressed in the temporal lobe (p-value 0.0058) of the cerebral cortex. This is the first study exploring the migraine risk of 17 functional variants in 12 genes among Saudi female migraineurs of Arab ancestry using whole-exome sequencing. Half of the significant genes were expressed in the temporal lobe, which expands migraine pathophysiology and early identification using biomarkers for research possibilities on personalised genetics.<\/jats:p>","DOI":"10.3390\/brainsci12111429","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T11:53:55Z","timestamp":1666612435000},"page":"1429","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Whole-Exome Sequencing Reveals Migraine-Associated Novel Functional Variants in Arab Ancestry Females: A Pilot Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0044-4758","authenticated-orcid":false,"given":"Johra","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia"},{"name":"Health and Basic Sciences Research Center, Majmaah University, Majmaah 11952, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0371-2367","authenticated-orcid":false,"given":"Lubna","family":"Al Asoom","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31541, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5402-1091","authenticated-orcid":false,"given":"Ahmad","family":"Al Sunni","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31541, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazish","family":"Rafique","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31541, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabia","family":"Latif","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31541, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majed","family":"Alabdali","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 31952, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-9210","authenticated-orcid":false,"given":"Azhar","family":"Alhariri","sequence":"additional","affiliation":[{"name":"Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majed","family":"Aloqaily","sequence":"additional","affiliation":[{"name":"Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9763-9446","authenticated-orcid":false,"given":"Sayed","family":"AbdulAzeez","sequence":"additional","affiliation":[{"name":"Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6976-5672","authenticated-orcid":false,"given":"Sadaf","family":"Jahan","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4423-8892","authenticated-orcid":false,"given":"Saeed","family":"Banawas","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah 11952, Saudi Arabia"},{"name":"Health and Basic Sciences Research Center, Majmaah University, Majmaah 11952, Saudi Arabia"},{"name":"Department of Biomedical Sciences, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7199-1540","authenticated-orcid":false,"given":"J. Francis","family":"Borgio","sequence":"additional","affiliation":[{"name":"Department of Genetic Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"},{"name":"Department of Epidemic Diseases Research, Institute for Research and Medical Consultations (IRMC), Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.jns.2016.11.071","article-title":"Migraine affects 1 in 10 people worldwide featuring recent rise: A systematic review and meta-analysis of community-based studies involving 6 million participants","volume":"372","author":"Woldeamanuel","year":"2017","journal-title":"J. Neurol. 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