{"title":"多发性硬化症的多基因易感性与学习成绩差的年轻人的工作记忆有关。","authors":"","doi":"10.1016/j.jns.2024.123138","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Multiple sclerosis (MS) is a complex disease with substantial heritability estimates. Besides typical clinical manifestations such as motor and sensory deficits, MS is characterized by structural and functional brain abnormalities, and by cognitive impairment such as decreased working memory (WM) performance.</p></div><div><h3>Objectives</h3><p>We investigated the possible link between the polygenic risk for MS and WM performance in healthy adults (18–35 years). Additionally, we addressed the relationship between polygenic risk for MS and white matter fractional anisotropy (FA).</p></div><div><h3>Methods</h3><p>We generated a polygenic risk score (PRS) of MS susceptibility and investigated its association with WM performance in 3282 healthy adults (two subsamples, <em>N</em><sub><em>1</em></sub> = 1803, <em>N</em><sub><em>2</em></sub> = 1479). The association between MS-PRS and FA was studied in the second subsample. MS severity PRS associations were also investigated for the WM and FA measurements.</p></div><div><h3>Results</h3><p>MS-PRS was significantly associated with WM performance within the 10% lowest WM-performing individuals (<em>p</em> = 0.001; <em>p</em><sub><em>FDR</em></sub> = 0.018). It was not significantly associated with any of the investigated FA measurements. MS severity PRS was significantly associated with brain-wide mean FA (<em>p</em> = 0.041) and showed suggestive associations with additional FA measurements.</p></div><div><h3>Conclusions</h3><p>By identifying a genetic link between MS and WM performance this study contributes to the understanding of the genetic complexity of MS, and hopefully to the possible identification of molecular pathways linked to cognitive deficits in MS. It also contributes to the understanding of genetic associations with MS severity, as these associations seem to involve distinct biological pathways compared to genetic variants linked to the overall risk of developing MS.</p></div>","PeriodicalId":17417,"journal":{"name":"Journal of the Neurological Sciences","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0022510X24002739/pdfft?md5=0f8af3a94345bd7c9682e9270c5f7fb2&pid=1-s2.0-S0022510X24002739-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Polygenic susceptibility for multiple sclerosis is associated with working memory in low-performing young adults\",\"authors\":\"\",\"doi\":\"10.1016/j.jns.2024.123138\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Multiple sclerosis (MS) is a complex disease with substantial heritability estimates. Besides typical clinical manifestations such as motor and sensory deficits, MS is characterized by structural and functional brain abnormalities, and by cognitive impairment such as decreased working memory (WM) performance.</p></div><div><h3>Objectives</h3><p>We investigated the possible link between the polygenic risk for MS and WM performance in healthy adults (18–35 years). Additionally, we addressed the relationship between polygenic risk for MS and white matter fractional anisotropy (FA).</p></div><div><h3>Methods</h3><p>We generated a polygenic risk score (PRS) of MS susceptibility and investigated its association with WM performance in 3282 healthy adults (two subsamples, <em>N</em><sub><em>1</em></sub> = 1803, <em>N</em><sub><em>2</em></sub> = 1479). The association between MS-PRS and FA was studied in the second subsample. MS severity PRS associations were also investigated for the WM and FA measurements.</p></div><div><h3>Results</h3><p>MS-PRS was significantly associated with WM performance within the 10% lowest WM-performing individuals (<em>p</em> = 0.001; <em>p</em><sub><em>FDR</em></sub> = 0.018). It was not significantly associated with any of the investigated FA measurements. MS severity PRS was significantly associated with brain-wide mean FA (<em>p</em> = 0.041) and showed suggestive associations with additional FA measurements.</p></div><div><h3>Conclusions</h3><p>By identifying a genetic link between MS and WM performance this study contributes to the understanding of the genetic complexity of MS, and hopefully to the possible identification of molecular pathways linked to cognitive deficits in MS. It also contributes to the understanding of genetic associations with MS severity, as these associations seem to involve distinct biological pathways compared to genetic variants linked to the overall risk of developing MS.</p></div>\",\"PeriodicalId\":17417,\"journal\":{\"name\":\"Journal of the Neurological Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-07-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0022510X24002739/pdfft?md5=0f8af3a94345bd7c9682e9270c5f7fb2&pid=1-s2.0-S0022510X24002739-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of the Neurological Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0022510X24002739\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Neurological Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0022510X24002739","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：多发性硬化症（MS）是一种复杂的疾病，遗传率很高。除了典型的临床表现（如运动和感觉障碍）外，多发性硬化症还表现为大脑结构和功能异常以及认知障碍（如工作记忆（WM）能力下降）：我们研究了多发性硬化症的多基因风险与健康成年人（18-35 岁）工作记忆能力之间可能存在的联系。此外，我们还探讨了多发性硬化症的多基因风险与白质分数各向异性（FA）之间的关系：方法：我们生成了多发性硬化症易感性的多基因风险评分（PRS），并调查了 3282 名健康成人（两个子样本，N1 = 1803，N2 = 1479）的多发性硬化症易感性与白质分数各向异性（FA）之间的关系。在第二个子样本中研究了 MS-PRS 与 FA 之间的关联。同时还研究了 MS 严重程度 PRS 与 WM 和 FA 测量的关联：MS-PRS与WM表现最低的10%个体的WM表现明显相关（p = 0.001; pFDR = 0.018）。它与所调查的任何 FA 测量结果均无明显关联。MS严重程度PRS与全脑平均FA显著相关（p = 0.041），并与其他FA测量结果显示出提示性关联：通过确定多发性硬化症与 WM 表现之间的遗传联系，本研究有助于了解多发性硬化症的遗传复杂性，并有望确定与多发性硬化症认知障碍有关的分子通路。它还有助于理解遗传与多发性硬化症严重程度的关系，因为与与多发性硬化症总体发病风险相关的遗传变异相比，这些关系似乎涉及不同的生物途径。
Polygenic susceptibility for multiple sclerosis is associated with working memory in low-performing young adults
Background
Multiple sclerosis (MS) is a complex disease with substantial heritability estimates. Besides typical clinical manifestations such as motor and sensory deficits, MS is characterized by structural and functional brain abnormalities, and by cognitive impairment such as decreased working memory (WM) performance.
Objectives
We investigated the possible link between the polygenic risk for MS and WM performance in healthy adults (18–35 years). Additionally, we addressed the relationship between polygenic risk for MS and white matter fractional anisotropy (FA).
Methods
We generated a polygenic risk score (PRS) of MS susceptibility and investigated its association with WM performance in 3282 healthy adults (two subsamples, N1 = 1803, N2 = 1479). The association between MS-PRS and FA was studied in the second subsample. MS severity PRS associations were also investigated for the WM and FA measurements.
Results
MS-PRS was significantly associated with WM performance within the 10% lowest WM-performing individuals (p = 0.001; pFDR = 0.018). It was not significantly associated with any of the investigated FA measurements. MS severity PRS was significantly associated with brain-wide mean FA (p = 0.041) and showed suggestive associations with additional FA measurements.
Conclusions
By identifying a genetic link between MS and WM performance this study contributes to the understanding of the genetic complexity of MS, and hopefully to the possible identification of molecular pathways linked to cognitive deficits in MS. It also contributes to the understanding of genetic associations with MS severity, as these associations seem to involve distinct biological pathways compared to genetic variants linked to the overall risk of developing MS.
期刊介绍：
The Journal of the Neurological Sciences provides a medium for the prompt publication of original articles in neurology and neuroscience from around the world. JNS places special emphasis on articles that: 1) provide guidance to clinicians around the world (Best Practices, Global Neurology); 2) report cutting-edge science related to neurology (Basic and Translational Sciences); 3) educate readers about relevant and practical clinical outcomes in neurology (Outcomes Research); and 4) summarize or editorialize the current state of the literature (Reviews, Commentaries, and Editorials).
JNS accepts most types of manuscripts for consideration including original research papers, short communications, reviews, book reviews, letters to the Editor, opinions and editorials. Topics considered will be from neurology-related fields that are of interest to practicing physicians around the world. Examples include neuromuscular diseases, demyelination, atrophies, dementia, neoplasms, infections, epilepsies, disturbances of consciousness, stroke and cerebral circulation, growth and development, plasticity and intermediary metabolism.
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