{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,12,24]],"date-time":"2022-12-24T05:52:40Z","timestamp":1671861160905},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:00:00Z","timestamp":1508198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,10,17]],"date-time":"2017-10-17T00:00:00Z","timestamp":1508198400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A recent genome-wide association study (GWAS) identified four genetic variants rs78726293, rs191260602, rs17035816 and rs7688285 in GLRB gene to be associated with panic disorder (PD) risk. In fact, GWAS is an important first step to investigate the genetics of human complex diseases. In order to translate into opportunities for new diagnostics and therapies, we must identify the genes perturbed by these four variants, and understand how these variant functionally contributes to the underlying disease pathogenesis. Here, we investigated the effect of these four genetic variants and the expression of three nearby genes including PDGFC, GLRB and GRIA2 in human brain tissues using the GTEx (version 6) and Braineac eQTLs datasets. In GTEx (version 6) dataset, the results showed that both rs17035816 and rs7688285 variants could significantly regulate PDGFC and GLRB gene expression. In Braineac dataset, the results showed that rs17035816 variant could significantly regulate GLRB and GRIA2 gene expression. We believe that these findings further provide important supplementary information about the regulating mechanisms of rs17035816 and rs7688285 variants in PD risk.<\/jats:p>","DOI":"10.1038\/s41598-017-13702-8","type":"journal-article","created":{"date-parts":[[2017,10,11]],"date-time":"2017-10-11T10:03:01Z","timestamp":1507716181000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GLRB variants regulate nearby gene expression in human brain tissues"],"prefix":"10.1038","volume":"7","author":[{"given":"Qing-jian","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming-feng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pi-da","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheng-jun","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-jing","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-jun","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao-liang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-yin","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,10,17]]},"reference":[{"key":"13702_CR1","doi-asserted-by":"crossref","unstructured":"Deckert, J. et al. GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder. Mol Psychiatry (2017).","DOI":"10.1016\/j.euroneuro.2016.09.607"},{"key":"13702_CR2","doi-asserted-by":"publisher","first-page":"D930","DOI":"10.1093\/nar\/gkr917","volume":"40","author":"LD Ward","year":"2012","unstructured":"Ward, L. D. & Kellis, M. HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res \n                           40, D930\u2013934 (2012).","journal-title":"Nucleic Acids Res"},{"issue":"2904","key":"13702_CR3","first-page":"e2901","volume":"36","author":"X Bao","year":"2015","unstructured":"Bao, X. et al. Cell adhesion molecule pathway genes are regulated by cis-regulatory SNPs and show significantly altered expression in Alzheimer\u2019s disease brains. Neurobiol Aging \n                           36(2904), e2901\u20132907 (2015).","journal-title":"Neurobiol Aging"},{"key":"13702_CR4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1509048112","volume":"112","author":"G Liu","year":"2015","unstructured":"Liu, G., Bao, X. & Wang, R. Expression quantitative trait loci regulate HNF4A and PTBP1 expression in human brains. Proc Natl Acad Sci USA \n                           112, E3975 (2015).","journal-title":"Proc Natl Acad Sci USA"},{"key":"13702_CR5","doi-asserted-by":"publisher","first-page":"E6321","DOI":"10.1073\/pnas.1614369113","volume":"113","author":"G Liu","year":"2016","unstructured":"Liu, G. et al. Cis-eQTLs regulate reduced LST1 gene and NCR3 gene expression and contribute to increased autoimmune disease risk. Proc Natl Acad Sci USA \n                           113, E6321\u2013E6322 (2016).","journal-title":"Proc Natl Acad Sci USA"},{"key":"13702_CR6","doi-asserted-by":"publisher","first-page":"E906","DOI":"10.1073\/pnas.1618520114","volume":"114","author":"G Liu","year":"2017","unstructured":"Liu, G., Hu, Y., Jin, S. & Jiang, Q. Genetic variant rs763361 regulates multiple sclerosis CD226 gene expression. Proc Natl Acad Sci U S A \n                           114, E906\u2013E907 (2017).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"13702_CR7","doi-asserted-by":"publisher","first-page":"4931","DOI":"10.1007\/s12035-015-9416-7","volume":"53","author":"G Liu","year":"2016","unstructured":"Liu, G. et al. Convergent Genetic and Expression Datasets Highlight TREM2 in Parkinson\u2019s Disease Susceptibility. Mol Neurobiol \n                           53, 4931\u20134938 (2016).","journal-title":"Mol Neurobiol"},{"key":"13702_CR8","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.2796","volume":"73","author":"Q Jiang","year":"2016","unstructured":"Jiang, Q., Hu, Y. & Liu, G. Association of Alzheimer Disease Susceptibility Variants and Gene Expression in the Human Brain. JAMA Neurol \n                           73, 1255 (2016).","journal-title":"JAMA Neurol"},{"key":"13702_CR9","doi-asserted-by":"crossref","unstructured":"Hu, Y., Jin, S., Cheng, L., Liu, G. & Jiang, Q. Autoimmune disease variants regulate GSDMB gene expression in human immune cells and whole blood. Proc Natl Acad Sci USA (2017).","DOI":"10.1073\/pnas.1712127114"},{"key":"13702_CR10","unstructured":"Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science \n                           348, 648\u2013660 (2015)."},{"key":"13702_CR11","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1007\/s12035-015-9670-8","volume":"54","author":"Q Jiang","year":"2017","unstructured":"Jiang, Q. et al. Alzheimer\u2019s Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells. Mol Neurobiol \n                           54, 594\u2013600 (2017).","journal-title":"Mol Neurobiol"},{"key":"13702_CR12","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1177\/1352458516649038","volume":"23","author":"G Liu","year":"2017","unstructured":"Liu, G. et al. Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways. Mult Scler \n                           23, 205\u2013212 (2017).","journal-title":"Mult Scler"},{"key":"13702_CR13","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.jns.2017.01.030","volume":"375","author":"Y Hu","year":"2017","unstructured":"Hu, Y. et al. GAB2 rs2373115 variant contributes to Alzheimer\u2019s disease risk specifically in European population. J Neurol Sci \n                           375, 18\u201322 (2017).","journal-title":"J Neurol Sci"},{"key":"13702_CR14","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/j.1471-4159.2011.07547.x","volume":"120","author":"G Liu","year":"2012","unstructured":"Liu, G. et al. Cell adhesion molecules contribute to Alzheimer\u2019s disease: multiple pathway analyses of two genome-wide association studies. 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Mol Neurobiol \n                           51, 1017\u20131023 (2015).","journal-title":"Mol Neurobiol"},{"key":"13702_CR19","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s00702-014-1260-9","volume":"122","author":"S Zhang","year":"2015","unstructured":"Zhang, S. et al. CLU rs2279590 polymorphism contributes to Alzheimer\u2019s disease susceptibility in Caucasian and Asian populations. J Neural Transm (Vienna) \n                           122, 433\u2013439 (2015).","journal-title":"J Neural Transm (Vienna)"},{"key":"13702_CR20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12035-014-8834-2","volume":"52","author":"H Chen","year":"2015","unstructured":"Chen, H. et al. Analyzing 54,936 Samples Supports the Association Between CD2AP rs9349407 Polymorphism and Alzheimer\u2019s Disease Susceptibility. Mol Neurobiol \n                           52, 1\u20137 (2015).","journal-title":"Mol Neurobiol"},{"key":"13702_CR21","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1007\/s12035-014-8880-9","volume":"52","author":"X Li","year":"2015","unstructured":"Li, X. et al. CD33rs3865444 Polymorphism Contributes to Alzheimer\u2019s Disease Susceptibility in Chinese, European, and North American Populations. Mol Neurobiol \n                           52, 414\u2013421 (2015).","journal-title":"Mol Neurobiol"},{"key":"13702_CR22","doi-asserted-by":"publisher","first-page":"4054","DOI":"10.1007\/s12035-015-9343-7","volume":"53","author":"Y Li","year":"2016","unstructured":"Li, Y. et al. CR1rs3818361 Polymorphism Contributes to Alzheimer\u2019s Disease Susceptibility in Chinese Population. Mol Neurobiol \n                           53, 4054\u20134059 (2016).","journal-title":"Mol Neurobiol"},{"key":"13702_CR23","doi-asserted-by":"crossref","unstructured":"Liu, G. et al. 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Measles contributes to rheumatoid arthritis: evidence from pathway and network analyses of genome-wide association studies. PLoS One \n                           8, e75951 (2013).","journal-title":"PLoS One"},{"key":"13702_CR27","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s00438-014-0945-y","volume":"290","author":"B Quan","year":"2015","unstructured":"Quan, B. et al. Pathway analysis of genome-wide association study and transcriptome data highlights new biological pathways in colorectal cancer. Mol Genet Genomics \n                           290, 603\u2013610 (2015).","journal-title":"Mol Genet Genomics"},{"key":"13702_CR28","doi-asserted-by":"publisher","DOI":"10.1038\/srep13025","volume":"5","author":"X Zhao","year":"2015","unstructured":"Zhao, X. et al. Pathway analysis of body mass index genome-wide association study highlights risk pathways in cardiovascular disease. 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Mol Neurobiol \n                           51, 361\u2013369 (2015).","journal-title":"Mol Neurobiol"},{"key":"13702_CR31","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1038\/ng.3654","volume":"48","author":"P Surendran","year":"2016","unstructured":"Surendran, P. et al. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension. Nat Genet \n                           48, 1151\u20131161 (2016).","journal-title":"Nat Genet"},{"key":"13702_CR32","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1038\/nn.3801","volume":"17","author":"A Ramasamy","year":"2014","unstructured":"Ramasamy, A. et al. Genetic variability in the regulation of gene expression in ten regions of the human brain. Nat Neurosci \n                           17, 1418\u20131428 (2014).","journal-title":"Nat Neurosci"},{"key":"13702_CR33","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s00401-016-1576-7","volume":"132","author":"M Allen","year":"2016","unstructured":"Allen, M. et al. Gene expression, methylation and neuropathology correlations at progressive supranuclear palsy risk loci. Acta Neuropathol \n                           132, 197\u2013211 (2016).","journal-title":"Acta Neuropathol"},{"key":"13702_CR34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1002707","volume":"8","author":"F Zou","year":"2012","unstructured":"Zou, F. et al. Brain expression genome-wide association study (eGWAS) identifies human disease-associated variants. PLoS Genet \n                           8, e1002707 (2012).","journal-title":"PLoS Genet"},{"key":"13702_CR35","unstructured":"The Genotype-Tissue Expression (GTEx) project. Nat Genet \n                           45, 580\u2013585 (2013)."},{"key":"13702_CR36","doi-asserted-by":"crossref","unstructured":"Liu, G. et al. Genetic Variants and Multiple Sclerosis Risk Gene SLC9A9 Expression in Distinct Human Brain Regions. Mol Neurobiol (2016).","DOI":"10.1007\/s12035-016-0208-5"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-13702-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-13702-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-13702-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T12:05:20Z","timestamp":1671797120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-13702-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,17]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["13702"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-13702-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,17]]},"assertion":[{"value":"21 June 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"13326"}}