{"title":"对20万名英国生物银行参与者进行外显子组测序，研究罕见家族性偏头痛综合征的基因变异及其与偏头痛的关系","authors":"Katherine Alexis Markel, David Curtis","doi":"10.1111/ahg.12484","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>A number of genes have been implicated in rare familial syndromes which have migraine as part of their phenotype but these genes have not previously been implicated in the common form of migraine.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Among exome-sequenced participants in the UK Biobank, we identified 7194 migraine cases with the remaining 193,433 participants classified as controls. We investigated rare variants in 10 genes previously reported to be implicated in conditions with migraine as a prominent part of the phenotype and carried out gene- and variant-based tests for association.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We found no evidence for association of these genes or variants with the common form of migraine seen in our subjects. In particular, a frameshift variant in <i>KCNK18</i>, p.(Phe139Trpfs*24), which had been shown to segregate with migraine with aura in a multiply affected pedigree, was found in 196 (0.10%) controls as well as in 10 (0.14%) cases (<i>χ</i><sup>2</sup> = 0.96, 1 df, <i>p</i> = 0.33).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Since there is no other reported evidence to implicate <i>KCNK18</i>, we conclude that this gene and its product, TRESK, should no longer be regarded as being involved in migraine aetiology. Overall, we do not find that rare, functional variants in genes previously implicated to be involved in familial syndromes including migraine as part of the phenotype make a contribution to the commoner forms of migraine observed in this population.</p>\n </section>\n </div>","PeriodicalId":8085,"journal":{"name":"Annals of Human Genetics","volume":"86 6","pages":"353-360"},"PeriodicalIF":1.0000,"publicationDate":"2022-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12484","citationCount":"2","resultStr":"{\"title\":\"Study of variants in genes implicated in rare familial migraine syndromes and their association with migraine in 200,000 exome-sequenced UK Biobank participants\",\"authors\":\"Katherine Alexis Markel, David Curtis\",\"doi\":\"10.1111/ahg.12484\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>A number of genes have been implicated in rare familial syndromes which have migraine as part of their phenotype but these genes have not previously been implicated in the common form of migraine.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Among exome-sequenced participants in the UK Biobank, we identified 7194 migraine cases with the remaining 193,433 participants classified as controls. We investigated rare variants in 10 genes previously reported to be implicated in conditions with migraine as a prominent part of the phenotype and carried out gene- and variant-based tests for association.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>We found no evidence for association of these genes or variants with the common form of migraine seen in our subjects. In particular, a frameshift variant in <i>KCNK18</i>, p.(Phe139Trpfs*24), which had been shown to segregate with migraine with aura in a multiply affected pedigree, was found in 196 (0.10%) controls as well as in 10 (0.14%) cases (<i>χ</i><sup>2</sup> = 0.96, 1 df, <i>p</i> = 0.33).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>Since there is no other reported evidence to implicate <i>KCNK18</i>, we conclude that this gene and its product, TRESK, should no longer be regarded as being involved in migraine aetiology. Overall, we do not find that rare, functional variants in genes previously implicated to be involved in familial syndromes including migraine as part of the phenotype make a contribution to the commoner forms of migraine observed in this population.</p>\\n </section>\\n </div>\",\"PeriodicalId\":8085,\"journal\":{\"name\":\"Annals of Human Genetics\",\"volume\":\"86 6\",\"pages\":\"353-360\"},\"PeriodicalIF\":1.0000,\"publicationDate\":\"2022-08-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahg.12484\",\"citationCount\":\"2\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Human Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/ahg.12484\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Human Genetics","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/ahg.12484","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 2
摘要
一些基因与偏头痛作为其表型的一部分的罕见家族性综合征有关，但这些基因以前没有与偏头痛的常见形式有关。方法:在英国生物银行外显子组测序的参与者中，我们确定了7194例偏头痛病例，其余193433例参与者归类为对照组。我们研究了先前报道的与偏头痛相关的10个基因的罕见变异，并进行了基于基因和变异的相关性测试。结果:在我们的研究对象中，我们没有发现这些基因或变异与常见形式的偏头痛相关的证据。特别是，KCNK18, p.(Phe139Trpfs*24)中的移码变异，在多重影响谱系中被证明与先兆偏头痛分离，在196例(0.10%)对照和10例(0.14%)病例中被发现(χ2 = 0.96, 1 df, p = 0.33)。由于没有其他证据表明KCNK18与偏头痛有关，我们得出结论，该基因及其产物TRESK不应再被认为与偏头痛病因有关。总的来说，我们没有发现先前涉及家族性综合征(包括偏头痛)的基因中罕见的功能性变异作为表型的一部分对该人群中观察到的常见形式的偏头痛有贡献。
Study of variants in genes implicated in rare familial migraine syndromes and their association with migraine in 200,000 exome-sequenced UK Biobank participants
Background
A number of genes have been implicated in rare familial syndromes which have migraine as part of their phenotype but these genes have not previously been implicated in the common form of migraine.
Methods
Among exome-sequenced participants in the UK Biobank, we identified 7194 migraine cases with the remaining 193,433 participants classified as controls. We investigated rare variants in 10 genes previously reported to be implicated in conditions with migraine as a prominent part of the phenotype and carried out gene- and variant-based tests for association.
Results
We found no evidence for association of these genes or variants with the common form of migraine seen in our subjects. In particular, a frameshift variant in KCNK18, p.(Phe139Trpfs*24), which had been shown to segregate with migraine with aura in a multiply affected pedigree, was found in 196 (0.10%) controls as well as in 10 (0.14%) cases (χ2 = 0.96, 1 df, p = 0.33).
Conclusions
Since there is no other reported evidence to implicate KCNK18, we conclude that this gene and its product, TRESK, should no longer be regarded as being involved in migraine aetiology. Overall, we do not find that rare, functional variants in genes previously implicated to be involved in familial syndromes including migraine as part of the phenotype make a contribution to the commoner forms of migraine observed in this population.
期刊介绍：
Annals of Human Genetics publishes material directly concerned with human genetics or the application of scientific principles and techniques to any aspect of human inheritance. Papers that describe work on other species that may be relevant to human genetics will also be considered. Mathematical models should include examples of application to data where possible.
Authors are welcome to submit Supporting Information, such as data sets or additional figures or tables, that will not be published in the print edition of the journal, but which will be viewable via the online edition and stored on the website.
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