Shared genetic architecture between neuroticism, coronary artery disease and cardiovascular risk factors
Neuroticism is associated with poor health, cardiovascular disease (CVD) risk factors and coronary artery disease (CAD). The conditional/conjunctional false discovery rate method (cond/conjFDR) was applied to genome wide association study (GWAS) summary statistics on neuroticism ( n = 432,109), CAD...
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| Veröffentlicht in: | Translational psychiatry 2021-06, Vol.11 (1), p.368-368, Article 368 |
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| creator | Torgersen, Kristin Bahrami, Shahram Frei, Oleksandr Shadrin, Alexey Connell, Kevin S. O’ Smeland, Olav B. Munkhaugen, John Djurovic, Srdjan Dammen, Toril Andreassen, Ole A. |
| description | Neuroticism is associated with poor health, cardiovascular disease (CVD) risk factors and coronary artery disease (CAD). The conditional/conjunctional false discovery rate method (cond/conjFDR) was applied to genome wide association study (GWAS) summary statistics on neuroticism (
n
= 432,109), CAD (
n
= 184,305) and 12 CVD risk factors (
n
= 188,577–339,224) to investigate genetic overlap between neuroticism and CAD and CVD risk factors. CondFDR analyses identified 729 genomic loci associated with neuroticism after conditioning on CAD and CVD risk factors. The conjFDR analyses revealed 345 loci jointly associated with neuroticism and CAD (
n
= 30), body mass index (BMI) (
n
= 96) or another CVD risk factor (
n
= 1–60). Several loci were jointly associated with neuroticism and multiple CVD risk factors. Seventeen of the shared loci with CAD and 61 of the shared loci with BMI are novel for neuroticism. 21 of 30 (70%) neuroticism risk alleles were associated with higher CAD risk. Functional analyses of the genes mapped to the shared loci implicated cell division, nuclear receptor, elastic fiber formation as well as starch and sucrose metabolism pathways. Our results indicate polygenic overlap between neuroticism and CAD and CVD risk factors, suggesting that genetic factors may partly cause the comorbidity. This gives new insight into the shared molecular genetic basis of these conditions. |
| doi_str_mv | 10.1038/s41398-021-01466-9 |
| format | Article |
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n
= 432,109), CAD (
n
= 184,305) and 12 CVD risk factors (
n
= 188,577–339,224) to investigate genetic overlap between neuroticism and CAD and CVD risk factors. CondFDR analyses identified 729 genomic loci associated with neuroticism after conditioning on CAD and CVD risk factors. The conjFDR analyses revealed 345 loci jointly associated with neuroticism and CAD (
n
= 30), body mass index (BMI) (
n
= 96) or another CVD risk factor (
n
= 1–60). Several loci were jointly associated with neuroticism and multiple CVD risk factors. Seventeen of the shared loci with CAD and 61 of the shared loci with BMI are novel for neuroticism. 21 of 30 (70%) neuroticism risk alleles were associated with higher CAD risk. Functional analyses of the genes mapped to the shared loci implicated cell division, nuclear receptor, elastic fiber formation as well as starch and sucrose metabolism pathways. Our results indicate polygenic overlap between neuroticism and CAD and CVD risk factors, suggesting that genetic factors may partly cause the comorbidity. This gives new insight into the shared molecular genetic basis of these conditions.</description><identifier>ISSN: 2158-3188</identifier><identifier>EISSN: 2158-3188</identifier><identifier>DOI: 10.1038/s41398-021-01466-9</identifier><identifier>PMID: 34226488</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>45/43 ; 692/53 ; 692/699/476 ; Behavioral Sciences ; Biological Psychology ; Cardiovascular disease ; Cell division ; Coronary vessels ; Gene loci ; Life Sciences & Biomedicine ; Medicine ; Medicine & Public Health ; Neurosciences ; Pharmacotherapy ; Psychiatry ; Risk factors ; Science & Technology</subject><ispartof>Translational psychiatry, 2021-06, Vol.11 (1), p.368-368, Article 368</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>8</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000672708300002</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c541t-3f6da083ff29d6ffc94ee6a5c1271366b6e2ae07b8345e9ab9d1ee046645ce943</citedby><cites>FETCH-LOGICAL-c541t-3f6da083ff29d6ffc94ee6a5c1271366b6e2ae07b8345e9ab9d1ee046645ce943</cites><orcidid>0000-0002-6865-8795 ; 0000-0002-1181-4128 ; 0000-0002-8140-8061 ; 0000-0002-7467-250X ; 0000-0002-3761-5215 ; 0000-0002-4461-3568</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/PMC8257646/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257646/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,26572,27929,27930,39262,39263,41125,42194,51581,53796,53798</link.rule.ids></links><search><creatorcontrib>Torgersen, Kristin</creatorcontrib><creatorcontrib>Bahrami, Shahram</creatorcontrib><creatorcontrib>Frei, Oleksandr</creatorcontrib><creatorcontrib>Shadrin, Alexey</creatorcontrib><creatorcontrib>Connell, Kevin S. O’</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 architecture between neuroticism, coronary artery disease and cardiovascular risk factors</title><title>Translational psychiatry</title><addtitle>Transl Psychiatry</addtitle><addtitle>TRANSL PSYCHIAT</addtitle><description>Neuroticism is associated with poor health, cardiovascular disease (CVD) risk factors and coronary artery disease (CAD). The conditional/conjunctional false discovery rate method (cond/conjFDR) was applied to genome wide association study (GWAS) summary statistics on neuroticism (
n
= 432,109), CAD (
n
= 184,305) and 12 CVD risk factors (
n
= 188,577–339,224) to investigate genetic overlap between neuroticism and CAD and CVD risk factors. CondFDR analyses identified 729 genomic loci associated with neuroticism after conditioning on CAD and CVD risk factors. The conjFDR analyses revealed 345 loci jointly associated with neuroticism and CAD (
n
= 30), body mass index (BMI) (
n
= 96) or another CVD risk factor (
n
= 1–60). Several loci were jointly associated with neuroticism and multiple CVD risk factors. Seventeen of the shared loci with CAD and 61 of the shared loci with BMI are novel for neuroticism. 21 of 30 (70%) neuroticism risk alleles were associated with higher CAD risk. Functional analyses of the genes mapped to the shared loci implicated cell division, nuclear receptor, elastic fiber formation as well as starch and sucrose metabolism pathways. Our results indicate polygenic overlap between neuroticism and CAD and CVD risk factors, suggesting that genetic factors may partly cause the comorbidity. 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O’</au><au>Smeland, Olav B.</au><au>Munkhaugen, John</au><au>Djurovic, Srdjan</au><au>Dammen, Toril</au><au>Andreassen, Ole A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Shared genetic architecture between neuroticism, coronary artery disease and cardiovascular risk factors</atitle><jtitle>Translational psychiatry</jtitle><stitle>Transl Psychiatry</stitle><stitle>TRANSL PSYCHIAT</stitle><date>2021-06-17</date><risdate>2021</risdate><volume>11</volume><issue>1</issue><spage>368</spage><epage>368</epage><pages>368-368</pages><artnum>368</artnum><issn>2158-3188</issn><eissn>2158-3188</eissn><abstract>Neuroticism is associated with poor health, cardiovascular disease (CVD) risk factors and coronary artery disease (CAD). The conditional/conjunctional false discovery rate method (cond/conjFDR) was applied to genome wide association study (GWAS) summary statistics on neuroticism (
n
= 432,109), CAD (
n
= 184,305) and 12 CVD risk factors (
n
= 188,577–339,224) to investigate genetic overlap between neuroticism and CAD and CVD risk factors. CondFDR analyses identified 729 genomic loci associated with neuroticism after conditioning on CAD and CVD risk factors. The conjFDR analyses revealed 345 loci jointly associated with neuroticism and CAD (
n
= 30), body mass index (BMI) (
n
= 96) or another CVD risk factor (
n
= 1–60). Several loci were jointly associated with neuroticism and multiple CVD risk factors. Seventeen of the shared loci with CAD and 61 of the shared loci with BMI are novel for neuroticism. 21 of 30 (70%) neuroticism risk alleles were associated with higher CAD risk. Functional analyses of the genes mapped to the shared loci implicated cell division, nuclear receptor, elastic fiber formation as well as starch and sucrose metabolism pathways. Our results indicate polygenic overlap between neuroticism and CAD and CVD risk factors, suggesting that genetic factors may partly cause the comorbidity. This gives new insight into the shared molecular genetic basis of these conditions.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34226488</pmid><doi>10.1038/s41398-021-01466-9</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-6865-8795</orcidid><orcidid>https://orcid.org/0000-0002-1181-4128</orcidid><orcidid>https://orcid.org/0000-0002-8140-8061</orcidid><orcidid>https://orcid.org/0000-0002-7467-250X</orcidid><orcidid>https://orcid.org/0000-0002-3761-5215</orcidid><orcidid>https://orcid.org/0000-0002-4461-3568</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 45/43 692/53 692/699/476 Behavioral Sciences Biological Psychology Cardiovascular disease Cell division Coronary vessels Gene loci Life Sciences & Biomedicine Medicine Medicine & Public Health Neurosciences Pharmacotherapy Psychiatry Risk factors Science & Technology |
| title | Shared genetic architecture between neuroticism, coronary artery disease and cardiovascular risk factors |
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