Polygenic risk associated with Alzheimer’s disease and other traits influences genes involved in T cell signaling and activation
IntroductionT cells, known for their ability to respond to an enormous variety of pathogens and other insults, are increasingly recognized as important mediators of pathology in neurodegeneration and other diseases. T cell gene expression phenotypes can be regulated by disease-associated genetic var...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1337831/full |
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| author | Dallin Dressman Dallin Dressman Shinya Tasaki Shinya Tasaki Lei Yu Lei Yu Julie Schneider Julie Schneider Julie Schneider David A. Bennett David A. Bennett Wassim Elyaman Wassim Elyaman Badri Vardarajan Badri Vardarajan Badri Vardarajan |
| author_facet | Dallin Dressman Dallin Dressman Shinya Tasaki Shinya Tasaki Lei Yu Lei Yu Julie Schneider Julie Schneider Julie Schneider David A. Bennett David A. Bennett Wassim Elyaman Wassim Elyaman Badri Vardarajan Badri Vardarajan Badri Vardarajan |
| author_sort | Dallin Dressman |
| collection | DOAJ |
| description | IntroductionT cells, known for their ability to respond to an enormous variety of pathogens and other insults, are increasingly recognized as important mediators of pathology in neurodegeneration and other diseases. T cell gene expression phenotypes can be regulated by disease-associated genetic variants. Many complex diseases are better represented by polygenic risk than by individual variants.MethodsWe first compute a polygenic risk score (PRS) for Alzheimer’s disease (AD) using genomic sequencing data from a cohort of Alzheimer’s disease (AD) patients and age-matched controls, and validate the AD PRS against clinical metrics in our cohort. We then calculate the PRS for several autoimmune disease, neurological disorder, and immune function traits, and correlate these PRSs with T cell gene expression data from our cohort. We compare PRS-associated genes across traits and four T cell subtypes.ResultsSeveral genes and biological pathways associated with the PRS for these traits relate to key T cell functions. The PRS-associated gene signature generally correlates positively for traits within a particular category (autoimmune disease, neurological disease, immune function) with the exception of stroke. The trait-associated gene expression signature for autoimmune disease traits was polarized towards CD4+ T cell subtypes.DiscussionOur findings show that polygenic risk for complex disease and immune function traits can have varying effects on T cell gene expression trends. Several PRS-associated genes are potential candidates for therapeutic modulation in T cells, and could be tested in in vitro applications using cells from patients bearing high or low polygenic risk for AD or other conditions. |
| first_indexed | 2024-04-24T19:47:22Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T19:47:22Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-646c5968fcb94a70ae74307220e0da112024-03-25T04:21:58ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13378311337831Polygenic risk associated with Alzheimer’s disease and other traits influences genes involved in T cell signaling and activationDallin Dressman0Dallin Dressman1Shinya Tasaki2Shinya Tasaki3Lei Yu4Lei Yu5Julie Schneider6Julie Schneider7Julie Schneider8David A. Bennett9David A. Bennett10Wassim Elyaman11Wassim Elyaman12Badri Vardarajan13Badri Vardarajan14Badri Vardarajan15Department of Neurology, Columbia University, New York, NY, United StatesThe Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, United StatesRush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, IL, United StatesDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, United StatesRush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, IL, United StatesDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, United StatesRush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, IL, United StatesDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, United StatesDepartment of Pathology, Rush University Medical Center, Chicago, IL, United StatesRush University Medical Center, Rush Alzheimer’s Disease Center, Chicago, IL, United StatesDepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL, United StatesDepartment of Neurology, Columbia University, New York, NY, United StatesThe Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, United StatesDepartment of Neurology, Columbia University, New York, NY, United StatesThe Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, United StatesCollege of Physicians and Surgeons, Columbia University, The New York Presbyterian Hospital, The Gertrude H. Sergievsky Center, New York, NY, United StatesIntroductionT cells, known for their ability to respond to an enormous variety of pathogens and other insults, are increasingly recognized as important mediators of pathology in neurodegeneration and other diseases. T cell gene expression phenotypes can be regulated by disease-associated genetic variants. Many complex diseases are better represented by polygenic risk than by individual variants.MethodsWe first compute a polygenic risk score (PRS) for Alzheimer’s disease (AD) using genomic sequencing data from a cohort of Alzheimer’s disease (AD) patients and age-matched controls, and validate the AD PRS against clinical metrics in our cohort. We then calculate the PRS for several autoimmune disease, neurological disorder, and immune function traits, and correlate these PRSs with T cell gene expression data from our cohort. We compare PRS-associated genes across traits and four T cell subtypes.ResultsSeveral genes and biological pathways associated with the PRS for these traits relate to key T cell functions. The PRS-associated gene signature generally correlates positively for traits within a particular category (autoimmune disease, neurological disease, immune function) with the exception of stroke. The trait-associated gene expression signature for autoimmune disease traits was polarized towards CD4+ T cell subtypes.DiscussionOur findings show that polygenic risk for complex disease and immune function traits can have varying effects on T cell gene expression trends. Several PRS-associated genes are potential candidates for therapeutic modulation in T cells, and could be tested in in vitro applications using cells from patients bearing high or low polygenic risk for AD or other conditions.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1337831/fullpolygenic risk scoreAlzheimer’s diseaseT cellsgene expressiongenotype phenotype correlationimmunology |
| spellingShingle | Dallin Dressman Dallin Dressman Shinya Tasaki Shinya Tasaki Lei Yu Lei Yu Julie Schneider Julie Schneider Julie Schneider David A. Bennett David A. Bennett Wassim Elyaman Wassim Elyaman Badri Vardarajan Badri Vardarajan Badri Vardarajan Polygenic risk associated with Alzheimer’s disease and other traits influences genes involved in T cell signaling and activation Frontiers in Immunology polygenic risk score Alzheimer’s disease T cells gene expression genotype phenotype correlation immunology |
| title | Polygenic risk associated with Alzheimer’s disease and other traits influences genes involved in T cell signaling and activation |
| title_full | Polygenic risk associated with Alzheimer’s disease and other traits influences genes involved in T cell signaling and activation |
| title_fullStr | Polygenic risk associated with Alzheimer’s disease and other traits influences genes involved in T cell signaling and activation |
| title_full_unstemmed | Polygenic risk associated with Alzheimer’s disease and other traits influences genes involved in T cell signaling and activation |
| title_short | Polygenic risk associated with Alzheimer’s disease and other traits influences genes involved in T cell signaling and activation |
| title_sort | polygenic risk associated with alzheimer s disease and other traits influences genes involved in t cell signaling and activation |
| topic | polygenic risk score Alzheimer’s disease T cells gene expression genotype phenotype correlation immunology |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1337831/full |
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