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Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer’s disease
BACKGROUND: Although genome-wide association studies (GWAS) have successfully located various genetic variants susceptible to Alzheimer’s Disease (AD), it is still unclear how specific variants interact with genes and tissues to elucidate pathologies associated with AD. Summary-data-based Mendelian...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161451/ https://www.ncbi.nlm.nih.gov/pubmed/35655140 http://dx.doi.org/10.1186/s12864-022-08584-8 |
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author | Lee, Brian Yao, Xiaohui Shen, Li |
author_facet | Lee, Brian Yao, Xiaohui Shen, Li |
author_sort | Lee, Brian |
collection | PubMed |
description | BACKGROUND: Although genome-wide association studies (GWAS) have successfully located various genetic variants susceptible to Alzheimer’s Disease (AD), it is still unclear how specific variants interact with genes and tissues to elucidate pathologies associated with AD. Summary-data-based Mendelian Randomization (SMR) addresses this problem through an instrumental variable approach that integrates data from independent GWAS and expression quantitative trait locus (eQTL) studies in order to infer a causal effect of gene expression on a trait. RESULTS: Our study employed the SMR approach to integrate a set of meta-analytic cis-eQTL information from the Genotype-Tissue Expression (GTEx), CommonMind Consortium (CMC), and Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) consortiums with three sets of meta-analysis AD GWAS results. CONCLUSIONS: Our analysis identified twelve total gene probes (associated with twelve distinct genes) with a significant association with AD. Four of these genes survived a test of pleiotropy from linkage (the HEIDI test).Three of these genes – RP11-385F7.1, PRSS36, and AC012146.7 – have not yet been reported differentially expressed in the brain in the context of AD, and thus are the novel findings warranting further investigation. |
format | Online Article Text |
id | pubmed-9161451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-91614512022-06-03 Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer’s disease Lee, Brian Yao, Xiaohui Shen, Li BMC Genomics Research BACKGROUND: Although genome-wide association studies (GWAS) have successfully located various genetic variants susceptible to Alzheimer’s Disease (AD), it is still unclear how specific variants interact with genes and tissues to elucidate pathologies associated with AD. Summary-data-based Mendelian Randomization (SMR) addresses this problem through an instrumental variable approach that integrates data from independent GWAS and expression quantitative trait locus (eQTL) studies in order to infer a causal effect of gene expression on a trait. RESULTS: Our study employed the SMR approach to integrate a set of meta-analytic cis-eQTL information from the Genotype-Tissue Expression (GTEx), CommonMind Consortium (CMC), and Religious Orders Study and Rush Memory and Aging Project (ROS/MAP) consortiums with three sets of meta-analysis AD GWAS results. CONCLUSIONS: Our analysis identified twelve total gene probes (associated with twelve distinct genes) with a significant association with AD. Four of these genes survived a test of pleiotropy from linkage (the HEIDI test).Three of these genes – RP11-385F7.1, PRSS36, and AC012146.7 – have not yet been reported differentially expressed in the brain in the context of AD, and thus are the novel findings warranting further investigation. BioMed Central 2022-06-02 /pmc/articles/PMC9161451/ /pubmed/35655140 http://dx.doi.org/10.1186/s12864-022-08584-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Lee, Brian Yao, Xiaohui Shen, Li Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer’s disease |
title | Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer’s disease |
title_full | Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer’s disease |
title_fullStr | Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer’s disease |
title_full_unstemmed | Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer’s disease |
title_short | Integrative analysis of summary data from GWAS and eQTL studies implicates genes differentially expressed in Alzheimer’s disease |
title_sort | integrative analysis of summary data from gwas and eqtl studies implicates genes differentially expressed in alzheimer’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161451/ https://www.ncbi.nlm.nih.gov/pubmed/35655140 http://dx.doi.org/10.1186/s12864-022-08584-8 |
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