Shared genetic loci between depression and cardiometabolic traits
Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here in...
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| Veröffentlicht in: | PLoS genetics 2022-05, Vol.18 (5), p.e1010161-e1010161 |
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| creator | Torgersen, Kristin Rahman, Zillur Bahrami, Shahram Hindley, Guy Frederick Lanyon Parker, Nadine Frei, Oleksandr Shadrin, Alexey O'Connell, Kevin S Tesli, Martin Smeland, Olav B Munkhaugen, John Djurovic, Srdjan Dammen, Toril Andreassen, Ole A |
| description | Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402-776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk. |
| doi_str_mv | 10.1371/journal.pgen.1010161 |
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The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402-776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk.</description><identifier>ISSN: 1553-7404</identifier><identifier>ISSN: 1553-7390</identifier><identifier>EISSN: 1553-7404</identifier><identifier>DOI: 10.1371/journal.pgen.1010161</identifier><identifier>PMID: 35560157</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biology and Life Sciences ; Blood pressure ; Body mass index ; C-reactive protein ; C-Reactive Protein - genetics ; Cardiovascular diseases ; Cardiovascular Diseases - genetics ; Cardiovascular system ; Cholesterol ; Coronary artery ; Coronary Artery Disease - genetics ; Depression - genetics ; Depression, Mental ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - genetics ; Epidemiology ; Ethics ; Gene loci ; Gene mapping ; Genetic aspects ; Genetic Loci ; Genetic Predisposition to Disease ; Genetic relationship ; Genome-wide association studies ; Genome-Wide Association Study ; Health aspects ; Heart diseases ; Humans ; Linolenic acid ; Lipids ; Medicine and Health Sciences ; Mental depression ; Metabolism ; Molecular modelling ; Phenotype ; Phenotypes ; Polygenic inheritance ; Polymorphism, Single Nucleotide - genetics ; Psychological aspects ; Quantitative trait loci ; Risk factors</subject><ispartof>PLoS genetics, 2022-05, Vol.18 (5), p.e1010161-e1010161</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Torgersen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>2022 Torgersen et al 2022 Torgersen et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c750t-bcf82984be4d8ec21750c64d86d9436367b558cfe552311b717645003a61a263</citedby><cites>FETCH-LOGICAL-c750t-bcf82984be4d8ec21750c64d86d9436367b558cfe552311b717645003a61a263</cites><orcidid>0000-0003-1666-4701 ; 0000-0002-8140-8061 ; 0000-0002-3761-5215 ; 0000-0001-9383-2161 ; 0000-0002-7467-250X ; 0000-0002-8369-0152 ; 0000-0002-4461-3568 ; 0000-0002-6427-2625 ; 0000-0002-6865-8795 ; 0000-0002-8179-2788 ; 0000-0002-1181-4128</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170110/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170110/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,26572,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35560157$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Flint, Jonathan</contributor><creatorcontrib>Torgersen, Kristin</creatorcontrib><creatorcontrib>Rahman, Zillur</creatorcontrib><creatorcontrib>Bahrami, Shahram</creatorcontrib><creatorcontrib>Hindley, Guy Frederick Lanyon</creatorcontrib><creatorcontrib>Parker, Nadine</creatorcontrib><creatorcontrib>Frei, Oleksandr</creatorcontrib><creatorcontrib>Shadrin, Alexey</creatorcontrib><creatorcontrib>O'Connell, Kevin S</creatorcontrib><creatorcontrib>Tesli, Martin</creatorcontrib><creatorcontrib>Smeland, Olav B</creatorcontrib><creatorcontrib>Munkhaugen, John</creatorcontrib><creatorcontrib>Djurovic, Srdjan</creatorcontrib><creatorcontrib>Dammen, Toril</creatorcontrib><creatorcontrib>Andreassen, Ole A</creatorcontrib><title>Shared genetic loci between depression and cardiometabolic traits</title><title>PLoS genetics</title><addtitle>PLoS Genet</addtitle><description>Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402-776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk.</description><subject>Biology and Life Sciences</subject><subject>Blood pressure</subject><subject>Body mass index</subject><subject>C-reactive protein</subject><subject>C-Reactive Protein - genetics</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Cardiovascular system</subject><subject>Cholesterol</subject><subject>Coronary artery</subject><subject>Coronary Artery Disease - genetics</subject><subject>Depression - genetics</subject><subject>Depression, Mental</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Epidemiology</subject><subject>Ethics</subject><subject>Gene loci</subject><subject>Gene mapping</subject><subject>Genetic aspects</subject><subject>Genetic Loci</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic relationship</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Health aspects</subject><subject>Heart diseases</subject><subject>Humans</subject><subject>Linolenic acid</subject><subject>Lipids</subject><subject>Medicine and Health Sciences</subject><subject>Mental depression</subject><subject>Metabolism</subject><subject>Molecular modelling</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Polygenic inheritance</subject><subject>Polymorphism, Single Nucleotide - 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Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Torgersen, Kristin</au><au>Rahman, Zillur</au><au>Bahrami, Shahram</au><au>Hindley, Guy Frederick Lanyon</au><au>Parker, Nadine</au><au>Frei, Oleksandr</au><au>Shadrin, Alexey</au><au>O'Connell, Kevin S</au><au>Tesli, Martin</au><au>Smeland, Olav B</au><au>Munkhaugen, John</au><au>Djurovic, Srdjan</au><au>Dammen, Toril</au><au>Andreassen, Ole A</au><au>Flint, Jonathan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Shared genetic loci between depression and cardiometabolic traits</atitle><jtitle>PLoS genetics</jtitle><addtitle>PLoS Genet</addtitle><date>2022-05-13</date><risdate>2022</risdate><volume>18</volume><issue>5</issue><spage>e1010161</spage><epage>e1010161</epage><pages>e1010161-e1010161</pages><issn>1553-7404</issn><issn>1553-7390</issn><eissn>1553-7404</eissn><abstract>Epidemiological and clinical studies have found associations between depression and cardiovascular disease risk factors, and coronary artery disease patients with depression have worse prognosis. The genetic relationship between depression and these cardiovascular phenotypes is not known. We here investigated overlap at the genome-wide level and in individual loci between depression, coronary artery disease and cardiovascular risk factors. We used the bivariate causal mixture model (MiXeR) to quantify genome-wide polygenic overlap and the conditional/conjunctional false discovery rate (pleioFDR) method to identify shared loci, based on genome-wide association study summary statistics on depression (n = 450,619), coronary artery disease (n = 502,713) and nine cardiovascular risk factors (n = 204,402-776,078). Genetic loci were functionally annotated using FUnctional Mapping and Annotation (FUMA). Of 13.9K variants influencing depression, 9.5K (SD 1.0K) were shared with body-mass index. Of 4.4K variants influencing systolic blood pressure, 2K were shared with depression. ConjFDR identified 79 unique loci associated with depression and coronary artery disease or cardiovascular risk factors. Six genomic loci were associated jointly with depression and coronary artery disease, 69 with blood pressure, 49 with lipids, 9 with type 2 diabetes and 8 with c-reactive protein at conjFDR < 0.05. Loci associated with increased risk for depression were also associated with increased risk of coronary artery disease and higher total cholesterol, low-density lipoprotein and c-reactive protein levels, while there was a mixed pattern of effect direction for the other risk factors. Functional analyses of the shared loci implicated metabolism of alpha-linolenic acid pathway for type 2 diabetes. Our results showed polygenic overlap between depression, coronary artery disease and several cardiovascular risk factors and suggest molecular mechanisms underlying the association between depression and increased cardiovascular disease risk.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35560157</pmid><doi>10.1371/journal.pgen.1010161</doi><tpages>e1010161</tpages><orcidid>https://orcid.org/0000-0003-1666-4701</orcidid><orcidid>https://orcid.org/0000-0002-8140-8061</orcidid><orcidid>https://orcid.org/0000-0002-3761-5215</orcidid><orcidid>https://orcid.org/0000-0001-9383-2161</orcidid><orcidid>https://orcid.org/0000-0002-7467-250X</orcidid><orcidid>https://orcid.org/0000-0002-8369-0152</orcidid><orcidid>https://orcid.org/0000-0002-4461-3568</orcidid><orcidid>https://orcid.org/0000-0002-6427-2625</orcidid><orcidid>https://orcid.org/0000-0002-6865-8795</orcidid><orcidid>https://orcid.org/0000-0002-8179-2788</orcidid><orcidid>https://orcid.org/0000-0002-1181-4128</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1553-7404 |
| ispartof | PLoS genetics, 2022-05, Vol.18 (5), p.e1010161-e1010161 |
| issn | 1553-7404 1553-7390 1553-7404 |
| language | eng |
| recordid | cdi_plos_journals_2677633043 |
| source | MEDLINE; NORA - Norwegian Open Research Archives; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS) Journals Open Access; PubMed Central |
| subjects | Biology and Life Sciences Blood pressure Body mass index C-reactive protein C-Reactive Protein - genetics Cardiovascular diseases Cardiovascular Diseases - genetics Cardiovascular system Cholesterol Coronary artery Coronary Artery Disease - genetics Depression - genetics Depression, Mental Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics Epidemiology Ethics Gene loci Gene mapping Genetic aspects Genetic Loci Genetic Predisposition to Disease Genetic relationship Genome-wide association studies Genome-Wide Association Study Health aspects Heart diseases Humans Linolenic acid Lipids Medicine and Health Sciences Mental depression Metabolism Molecular modelling Phenotype Phenotypes Polygenic inheritance Polymorphism, Single Nucleotide - genetics Psychological aspects Quantitative trait loci Risk factors |
| title | Shared genetic loci between depression and cardiometabolic traits |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T19%3A13%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Shared%20genetic%20loci%20between%20depression%20and%20cardiometabolic%20traits&rft.jtitle=PLoS%20genetics&rft.au=Torgersen,%20Kristin&rft.date=2022-05-13&rft.volume=18&rft.issue=5&rft.spage=e1010161&rft.epage=e1010161&rft.pages=e1010161-e1010161&rft.issn=1553-7404&rft.eissn=1553-7404&rft_id=info:doi/10.1371/journal.pgen.1010161&rft_dat=%3Cgale_plos_%3EA705774323%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2677633043&rft_id=info:pmid/35560157&rft_galeid=A705774323&rft_doaj_id=oai_doaj_org_article_5a79f08b00a84586ac3791821276945e&rfr_iscdi=true |