Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq–Afghanistan era veterans
Abstract Background Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing traumatic events. A genome-wide association study (GWAS) design was used to identify genetic risk factors for PTSD within a multi-racial sample primarily composed of U.S. veterans....
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| Veröffentlicht in: | Journal of affective disorders 2015-09, Vol.184, p.225-234 |
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| creator | Ashley-Koch, Allison E Garrett, Melanie E Gibson, Jason Liu, Yutao Dennis, Michelle F Kimbrel, Nathan A Beckham, Jean C Hauser, Michael A |
| description | Abstract Background Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing traumatic events. A genome-wide association study (GWAS) design was used to identify genetic risk factors for PTSD within a multi-racial sample primarily composed of U.S. veterans. Methods Participants were recruited at multiple medical centers, and structured interviews were used to establish diagnoses. Genotypes were generated using three Illumina platforms and imputed with global reference data to create a common set of SNPs. SNPs that increased risk for PTSD were identified with logistic regression, while controlling for gender, trauma severity, and population substructure. Analyses were run separately in non-Hispanic black (NHB; n =949) and non-Hispanic white (NHW; n =759) participants. Meta-analysis was used to combine results from the two subsets. Results SNPs within several interesting candidate genes were nominally significant. Within the NHB subset, the most significant genes were UNC13C and DSCAM . Within the NHW subset, the most significant genes were TBC1D2 , SDC2 and PCDH7 . In addition, PRKG1 and DDX60L were identified through meta-analysis. The top genes for the three analyses have been previously implicated in neurologic processes consistent with a role in PTSD. Pathway analysis of the top genes identified alternative splicing as the top GO term in all three analyses (FDR q |
| doi_str_mv | 10.1016/j.jad.2015.03.049 |
| format | Article |
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A genome-wide association study (GWAS) design was used to identify genetic risk factors for PTSD within a multi-racial sample primarily composed of U.S. veterans. Methods Participants were recruited at multiple medical centers, and structured interviews were used to establish diagnoses. Genotypes were generated using three Illumina platforms and imputed with global reference data to create a common set of SNPs. SNPs that increased risk for PTSD were identified with logistic regression, while controlling for gender, trauma severity, and population substructure. Analyses were run separately in non-Hispanic black (NHB; n =949) and non-Hispanic white (NHW; n =759) participants. Meta-analysis was used to combine results from the two subsets. Results SNPs within several interesting candidate genes were nominally significant. Within the NHB subset, the most significant genes were UNC13C and DSCAM . Within the NHW subset, the most significant genes were TBC1D2 , SDC2 and PCDH7 . In addition, PRKG1 and DDX60L were identified through meta-analysis. The top genes for the three analyses have been previously implicated in neurologic processes consistent with a role in PTSD. Pathway analysis of the top genes identified alternative splicing as the top GO term in all three analyses (FDR q <3.5×10−5 ). Limitations No individual SNPs met genome-wide significance in the analyses. Conclusions This multi-racial PTSD GWAS identified biologically plausible candidate genes and suggests that post-transcriptional regulation may be important to the pathology of PTSD; however, replication of these findings is needed.</description><identifier>ISSN: 0165-0327</identifier><identifier>EISSN: 1573-2517</identifier><identifier>DOI: 10.1016/j.jad.2015.03.049</identifier><identifier>PMID: 26114229</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adult ; Afghan Campaign 2001 ; African Americans - genetics ; Alternative Splicing - genetics ; Cohort Studies ; Combat exposure ; European Continental Ancestry Group - genetics ; Female ; Geneenvironment interaction ; Genetic Predisposition to Disease - genetics ; Genome-Wide Association Study ; Genotype ; Humans ; Iraq War, 2003-2011 ; Male ; Meta-analysis ; Polymorphism, Single Nucleotide - genetics ; Posttraumatic stress disorder ; Psychiatry ; Stress Disorders, Post-Traumatic - genetics ; United States ; Veterans - psychology</subject><ispartof>Journal of affective disorders, 2015-09, Vol.184, p.225-234</ispartof><rights>Elsevier B.V.</rights><rights>2015 Elsevier B.V.</rights><rights>Copyright © 2015 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c539t-8431bc11aa459a95bd7f88a968a9cb15a3c6619ce0cfed73a22897dfdbab35b3</citedby><cites>FETCH-LOGICAL-c539t-8431bc11aa459a95bd7f88a968a9cb15a3c6619ce0cfed73a22897dfdbab35b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jad.2015.03.049$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26114229$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ashley-Koch, Allison E</creatorcontrib><creatorcontrib>Garrett, Melanie E</creatorcontrib><creatorcontrib>Gibson, Jason</creatorcontrib><creatorcontrib>Liu, Yutao</creatorcontrib><creatorcontrib>Dennis, Michelle F</creatorcontrib><creatorcontrib>Kimbrel, Nathan A</creatorcontrib><creatorcontrib>Beckham, Jean C</creatorcontrib><creatorcontrib>Hauser, Michael A</creatorcontrib><creatorcontrib>,</creatorcontrib><creatorcontrib>Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup</creatorcontrib><title>Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq–Afghanistan era veterans</title><title>Journal of affective disorders</title><addtitle>J Affect Disord</addtitle><description>Abstract Background Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing traumatic events. A genome-wide association study (GWAS) design was used to identify genetic risk factors for PTSD within a multi-racial sample primarily composed of U.S. veterans. Methods Participants were recruited at multiple medical centers, and structured interviews were used to establish diagnoses. Genotypes were generated using three Illumina platforms and imputed with global reference data to create a common set of SNPs. SNPs that increased risk for PTSD were identified with logistic regression, while controlling for gender, trauma severity, and population substructure. Analyses were run separately in non-Hispanic black (NHB; n =949) and non-Hispanic white (NHW; n =759) participants. Meta-analysis was used to combine results from the two subsets. Results SNPs within several interesting candidate genes were nominally significant. Within the NHB subset, the most significant genes were UNC13C and DSCAM . Within the NHW subset, the most significant genes were TBC1D2 , SDC2 and PCDH7 . In addition, PRKG1 and DDX60L were identified through meta-analysis. The top genes for the three analyses have been previously implicated in neurologic processes consistent with a role in PTSD. Pathway analysis of the top genes identified alternative splicing as the top GO term in all three analyses (FDR q <3.5×10−5 ). Limitations No individual SNPs met genome-wide significance in the analyses. Conclusions This multi-racial PTSD GWAS identified biologically plausible candidate genes and suggests that post-transcriptional regulation may be important to the pathology of PTSD; however, replication of these findings is needed.</description><subject>Adult</subject><subject>Afghan Campaign 2001</subject><subject>African Americans - genetics</subject><subject>Alternative Splicing - genetics</subject><subject>Cohort Studies</subject><subject>Combat exposure</subject><subject>European Continental Ancestry Group - genetics</subject><subject>Female</subject><subject>Geneenvironment interaction</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genome-Wide Association Study</subject><subject>Genotype</subject><subject>Humans</subject><subject>Iraq War, 2003-2011</subject><subject>Male</subject><subject>Meta-analysis</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Posttraumatic stress disorder</subject><subject>Psychiatry</subject><subject>Stress Disorders, Post-Traumatic - genetics</subject><subject>United States</subject><subject>Veterans - psychology</subject><issn>0165-0327</issn><issn>1573-2517</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9Uk1v1DAQjRCILoUfwAXlyCXBE8f5EFKlqqKlUiUO9G5N7EnXIbG3drJob_wH_mF_CY62VMCBgzXS-L1nz3uTJG-B5cCg-jDkA-q8YCByxnNWts-SDYiaZ4WA-nmyiRiRMV7UJ8mrEAbGWNXW7GVyUlQAZVG0m2S6Iusmyr4bTSmG4JTB2TibhnnRh9T16c6Fefa4TLGvYttTCKk2wXlNPjU2xVS5rfPzCr72eP_w4-d5f7dFa8KMNiWP6Z7mWGx4nbzocQz05rGeJreXn24vPmc3X66uL85vMiV4O2dNyaFTAIilaLEVna77psG2ikd1IJCrqoJWEVM96ZpjUTRtrXvdYcdFx0-Ts6Psbukm0opsHGCUO28m9Afp0Mi_b6zZyju3l2X0pxYiCrx_FPDufqEwy8kEReOIltwSJNSMASsBigiFI1R5F4Kn_ukZYHJNSQ4ypiTXlCTjMqYUOe_-_N8T43csEfDxCKBo0t6Ql0EZsoq08aRmqZ35r_zZP2w1GmsUjt_oQGFwi7fRfQkyFJLJr-uarFsCIk7VNJz_Atn0vAI</recordid><startdate>20150915</startdate><enddate>20150915</enddate><creator>Ashley-Koch, Allison E</creator><creator>Garrett, Melanie E</creator><creator>Gibson, Jason</creator><creator>Liu, Yutao</creator><creator>Dennis, Michelle F</creator><creator>Kimbrel, Nathan A</creator><creator>Beckham, Jean C</creator><creator>Hauser, Michael A</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150915</creationdate><title>Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq–Afghanistan era veterans</title><author>Ashley-Koch, Allison E ; Garrett, Melanie E ; Gibson, Jason ; Liu, Yutao ; Dennis, Michelle F ; Kimbrel, Nathan A ; Beckham, Jean C ; Hauser, Michael A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c539t-8431bc11aa459a95bd7f88a968a9cb15a3c6619ce0cfed73a22897dfdbab35b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Afghan Campaign 2001</topic><topic>African Americans - genetics</topic><topic>Alternative Splicing - genetics</topic><topic>Cohort Studies</topic><topic>Combat exposure</topic><topic>European Continental Ancestry Group - genetics</topic><topic>Female</topic><topic>Geneenvironment interaction</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genome-Wide Association Study</topic><topic>Genotype</topic><topic>Humans</topic><topic>Iraq War, 2003-2011</topic><topic>Male</topic><topic>Meta-analysis</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>Posttraumatic stress disorder</topic><topic>Psychiatry</topic><topic>Stress Disorders, Post-Traumatic - genetics</topic><topic>United States</topic><topic>Veterans - psychology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ashley-Koch, Allison E</creatorcontrib><creatorcontrib>Garrett, Melanie E</creatorcontrib><creatorcontrib>Gibson, Jason</creatorcontrib><creatorcontrib>Liu, Yutao</creatorcontrib><creatorcontrib>Dennis, Michelle F</creatorcontrib><creatorcontrib>Kimbrel, Nathan A</creatorcontrib><creatorcontrib>Beckham, Jean C</creatorcontrib><creatorcontrib>Hauser, Michael A</creatorcontrib><creatorcontrib>,</creatorcontrib><creatorcontrib>Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of affective disorders</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ashley-Koch, Allison E</au><au>Garrett, Melanie E</au><au>Gibson, Jason</au><au>Liu, Yutao</au><au>Dennis, Michelle F</au><au>Kimbrel, Nathan A</au><au>Beckham, Jean C</au><au>Hauser, Michael A</au><aucorp>,</aucorp><aucorp>Veterans Affairs Mid-Atlantic Mental Illness Research, Education, and Clinical Center Workgroup</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq–Afghanistan era veterans</atitle><jtitle>Journal of affective disorders</jtitle><addtitle>J Affect Disord</addtitle><date>2015-09-15</date><risdate>2015</risdate><volume>184</volume><spage>225</spage><epage>234</epage><pages>225-234</pages><issn>0165-0327</issn><eissn>1573-2517</eissn><abstract>Abstract Background Posttraumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing traumatic events. A genome-wide association study (GWAS) design was used to identify genetic risk factors for PTSD within a multi-racial sample primarily composed of U.S. veterans. Methods Participants were recruited at multiple medical centers, and structured interviews were used to establish diagnoses. Genotypes were generated using three Illumina platforms and imputed with global reference data to create a common set of SNPs. SNPs that increased risk for PTSD were identified with logistic regression, while controlling for gender, trauma severity, and population substructure. Analyses were run separately in non-Hispanic black (NHB; n =949) and non-Hispanic white (NHW; n =759) participants. Meta-analysis was used to combine results from the two subsets. Results SNPs within several interesting candidate genes were nominally significant. Within the NHB subset, the most significant genes were UNC13C and DSCAM . Within the NHW subset, the most significant genes were TBC1D2 , SDC2 and PCDH7 . In addition, PRKG1 and DDX60L were identified through meta-analysis. The top genes for the three analyses have been previously implicated in neurologic processes consistent with a role in PTSD. Pathway analysis of the top genes identified alternative splicing as the top GO term in all three analyses (FDR q <3.5×10−5 ). Limitations No individual SNPs met genome-wide significance in the analyses. Conclusions This multi-racial PTSD GWAS identified biologically plausible candidate genes and suggests that post-transcriptional regulation may be important to the pathology of PTSD; however, replication of these findings is needed.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>26114229</pmid><doi>10.1016/j.jad.2015.03.049</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Afghan Campaign 2001 African Americans - genetics Alternative Splicing - genetics Cohort Studies Combat exposure European Continental Ancestry Group - genetics Female Geneenvironment interaction Genetic Predisposition to Disease - genetics Genome-Wide Association Study Genotype Humans Iraq War, 2003-2011 Male Meta-analysis Polymorphism, Single Nucleotide - genetics Posttraumatic stress disorder Psychiatry Stress Disorders, Post-Traumatic - genetics United States Veterans - psychology |
| title | Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq–Afghanistan era veterans |
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