Coronary Artery Disease–Associated and Longevity-Associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living With Human Immunodeficiency Virus: The Swiss HIV Cohort Study
Abstract Background Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with human immunodeficiency virus (HIV) (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRSs) and by consid...
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| Veröffentlicht in: | Clinical infectious diseases 2021-11, Vol.73 (9), p.1597-1604 |
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| creator | Schoepf, Isabella C Thorball, Christian W Ledergerber, Bruno Engel, Tanja Raffenberg, Marieke Kootstra, Neeltje A Reiss, Peter Hasse, Barbara Marzolini, Catia Thurnheer, Christine Seneghini, Marco Bernasconi, Enos Cavassini, Matthias Buvelot, Hélène Kouyos, Roger Günthard, Huldrych F Fellay, Jacques Tarr, Philip E |
| description | Abstract
Background
Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with human immunodeficiency virus (HIV) (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRSs) and by considering genetic variants associated with successful aging and longevity.
Methods
In the Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (ORs) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRSs. PRSs were built from CAD-associated single-nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both.
Results
We included 269 patients with CAD events between 2000 and 2017 (median age, 54 years; 87% male; 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (ie, traditional and HIV-related) risk factors and PRSs, built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (P |
| doi_str_mv | 10.1093/cid/ciab521 |
| format | Article |
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Background
Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with human immunodeficiency virus (HIV) (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRSs) and by considering genetic variants associated with successful aging and longevity.
Methods
In the Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (ORs) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRSs. PRSs were built from CAD-associated single-nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both.
Results
We included 269 patients with CAD events between 2000 and 2017 (median age, 54 years; 87% male; 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (ie, traditional and HIV-related) risk factors and PRSs, built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (P < .001). Participants with the most unfavorable clinical risk factor profile (top quintile) had an adjusted CAD-OR of 17.82 (95% confidence interval [CI], 8.19–38.76), compared with participants in the bottom quintile. Participants with the most unfavorable CAD-PRSs (top quintile) had an adjusted CAD-OR of 3.17 (95% CI, 1.74–5.79), compared with the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had an adjusted CAD-OR of 3.67 (95% CI, 2.00–6.73), compared with the bottom quintile.
Conclusions
In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related, and genetic risk factors provided the most powerful CAD prediction.
Genetic background is associated with coronary artery disease (CAD) events. People living with human immunodeficiency virus have accentuated aging. Adding longevity-associated genetic variants to an individual polygenic risk score based on CAD-associated variants improves prediction of CAD events.</description><identifier>ISSN: 1058-4838</identifier><identifier>EISSN: 1537-6591</identifier><identifier>DOI: 10.1093/cid/ciab521</identifier><identifier>PMID: 34091660</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Cohort Studies ; Coronary Artery Disease - epidemiology ; Coronary Artery Disease - genetics ; Female ; Genetic Predisposition to Disease ; HIV ; HIV Infections - complications ; HIV Infections - epidemiology ; Humans ; Longevity - genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors ; Switzerland - epidemiology</subject><ispartof>Clinical infectious diseases, 2021-11, Vol.73 (9), p.1597-1604</ispartof><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c357t-7f4cf1792d645134611ec42374bbe02822fed022d176195918d9eb25ff2af8a93</citedby><cites>FETCH-LOGICAL-c357t-7f4cf1792d645134611ec42374bbe02822fed022d176195918d9eb25ff2af8a93</cites><orcidid>0000-0002-2312-7050 ; 0000-0003-0933-7833</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1584,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34091660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schoepf, Isabella C</creatorcontrib><creatorcontrib>Thorball, Christian W</creatorcontrib><creatorcontrib>Ledergerber, Bruno</creatorcontrib><creatorcontrib>Engel, Tanja</creatorcontrib><creatorcontrib>Raffenberg, Marieke</creatorcontrib><creatorcontrib>Kootstra, Neeltje A</creatorcontrib><creatorcontrib>Reiss, Peter</creatorcontrib><creatorcontrib>Hasse, Barbara</creatorcontrib><creatorcontrib>Marzolini, Catia</creatorcontrib><creatorcontrib>Thurnheer, Christine</creatorcontrib><creatorcontrib>Seneghini, Marco</creatorcontrib><creatorcontrib>Bernasconi, Enos</creatorcontrib><creatorcontrib>Cavassini, Matthias</creatorcontrib><creatorcontrib>Buvelot, Hélène</creatorcontrib><creatorcontrib>Kouyos, Roger</creatorcontrib><creatorcontrib>Günthard, Huldrych F</creatorcontrib><creatorcontrib>Fellay, Jacques</creatorcontrib><creatorcontrib>Tarr, Philip E</creatorcontrib><creatorcontrib>Swiss HIV Cohort Study</creatorcontrib><creatorcontrib>Swiss HIV Cohort Study</creatorcontrib><title>Coronary Artery Disease–Associated and Longevity-Associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living With Human Immunodeficiency Virus: The Swiss HIV Cohort Study</title><title>Clinical infectious diseases</title><addtitle>Clin Infect Dis</addtitle><description>Abstract
Background
Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with human immunodeficiency virus (HIV) (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRSs) and by considering genetic variants associated with successful aging and longevity.
Methods
In the Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (ORs) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRSs. PRSs were built from CAD-associated single-nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both.
Results
We included 269 patients with CAD events between 2000 and 2017 (median age, 54 years; 87% male; 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (ie, traditional and HIV-related) risk factors and PRSs, built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (P < .001). Participants with the most unfavorable clinical risk factor profile (top quintile) had an adjusted CAD-OR of 17.82 (95% confidence interval [CI], 8.19–38.76), compared with participants in the bottom quintile. Participants with the most unfavorable CAD-PRSs (top quintile) had an adjusted CAD-OR of 3.17 (95% CI, 1.74–5.79), compared with the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had an adjusted CAD-OR of 3.67 (95% CI, 2.00–6.73), compared with the bottom quintile.
Conclusions
In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related, and genetic risk factors provided the most powerful CAD prediction.
Genetic background is associated with coronary artery disease (CAD) events. People living with human immunodeficiency virus have accentuated aging. Adding longevity-associated genetic variants to an individual polygenic risk score based on CAD-associated variants improves prediction of CAD events.</description><subject>Cohort Studies</subject><subject>Coronary Artery Disease - epidemiology</subject><subject>Coronary Artery Disease - genetics</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>HIV</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - epidemiology</subject><subject>Humans</subject><subject>Longevity - genetics</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Factors</subject><subject>Switzerland - epidemiology</subject><issn>1058-4838</issn><issn>1537-6591</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2KE0EUhRtRnHF05V7uSgRprZ-u_nEX4owJBAxmHJdNp-pWUpquylRVZ-id7-Cr-QQ-iSWJ4kYXl3PhfpwL52TZU0peUdLw19KoNN1aMHovO6eCV3kpGno_7UTUeVHz-ix7FMJnQiitiXiYnfGCNLQsyXn2feq8s50fYeIjJnlrAnYBf3z9NgnBJd-ICjqrYOHsBg8mjvlfh6XbjRu0RsIHE77ASjqPAbTzsPSojIzGWXAa_vEFLg9oYwBjYYk-OBtgYQ7GbuCTiVuYDX1nYd73g3UKtZEGrRzhxvghvIHrLcLqzoQAs_lN-rB1PsIqDmp8nD3Q3S7gk5NeZB-vLq-ns3zx_t18Olnkkosq5pUupKZVw1RZCMqLklKUBeNVsV4jYTVjGhVhTNGqpE2KtFYNrpnQmnW67hp-kb04-u69ux0wxLY3QeJu11l0Q2iZ4DUpqlLwhL48otK7EDzqdu9NnxJpKWl_1dimGttTjYl-djIe1j2qP-zv3hLw_Ai4Yf9fp5-ZgqtP</recordid><startdate>20211102</startdate><enddate>20211102</enddate><creator>Schoepf, Isabella C</creator><creator>Thorball, Christian W</creator><creator>Ledergerber, Bruno</creator><creator>Engel, Tanja</creator><creator>Raffenberg, Marieke</creator><creator>Kootstra, Neeltje A</creator><creator>Reiss, Peter</creator><creator>Hasse, Barbara</creator><creator>Marzolini, Catia</creator><creator>Thurnheer, Christine</creator><creator>Seneghini, Marco</creator><creator>Bernasconi, Enos</creator><creator>Cavassini, Matthias</creator><creator>Buvelot, Hélène</creator><creator>Kouyos, Roger</creator><creator>Günthard, Huldrych F</creator><creator>Fellay, Jacques</creator><creator>Tarr, Philip E</creator><general>Oxford University Press</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><orcidid>https://orcid.org/0000-0002-2312-7050</orcidid><orcidid>https://orcid.org/0000-0003-0933-7833</orcidid></search><sort><creationdate>20211102</creationdate><title>Coronary Artery Disease–Associated and Longevity-Associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living With Human Immunodeficiency Virus: The Swiss HIV Cohort Study</title><author>Schoepf, Isabella C ; Thorball, Christian W ; Ledergerber, Bruno ; Engel, Tanja ; Raffenberg, Marieke ; Kootstra, Neeltje A ; Reiss, Peter ; Hasse, Barbara ; Marzolini, Catia ; Thurnheer, Christine ; Seneghini, Marco ; Bernasconi, Enos ; Cavassini, Matthias ; Buvelot, Hélène ; Kouyos, Roger ; Günthard, Huldrych F ; Fellay, Jacques ; Tarr, Philip E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c357t-7f4cf1792d645134611ec42374bbe02822fed022d176195918d9eb25ff2af8a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Cohort Studies</topic><topic>Coronary Artery Disease - epidemiology</topic><topic>Coronary Artery Disease - genetics</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>HIV</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - epidemiology</topic><topic>Humans</topic><topic>Longevity - genetics</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Factors</topic><topic>Switzerland - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schoepf, Isabella C</creatorcontrib><creatorcontrib>Thorball, Christian W</creatorcontrib><creatorcontrib>Ledergerber, Bruno</creatorcontrib><creatorcontrib>Engel, Tanja</creatorcontrib><creatorcontrib>Raffenberg, Marieke</creatorcontrib><creatorcontrib>Kootstra, Neeltje A</creatorcontrib><creatorcontrib>Reiss, Peter</creatorcontrib><creatorcontrib>Hasse, Barbara</creatorcontrib><creatorcontrib>Marzolini, Catia</creatorcontrib><creatorcontrib>Thurnheer, Christine</creatorcontrib><creatorcontrib>Seneghini, Marco</creatorcontrib><creatorcontrib>Bernasconi, Enos</creatorcontrib><creatorcontrib>Cavassini, Matthias</creatorcontrib><creatorcontrib>Buvelot, Hélène</creatorcontrib><creatorcontrib>Kouyos, Roger</creatorcontrib><creatorcontrib>Günthard, Huldrych F</creatorcontrib><creatorcontrib>Fellay, Jacques</creatorcontrib><creatorcontrib>Tarr, Philip E</creatorcontrib><creatorcontrib>Swiss HIV Cohort Study</creatorcontrib><creatorcontrib>Swiss HIV Cohort Study</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><jtitle>Clinical infectious diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schoepf, Isabella C</au><au>Thorball, Christian W</au><au>Ledergerber, Bruno</au><au>Engel, Tanja</au><au>Raffenberg, Marieke</au><au>Kootstra, Neeltje A</au><au>Reiss, Peter</au><au>Hasse, Barbara</au><au>Marzolini, Catia</au><au>Thurnheer, Christine</au><au>Seneghini, Marco</au><au>Bernasconi, Enos</au><au>Cavassini, Matthias</au><au>Buvelot, Hélène</au><au>Kouyos, Roger</au><au>Günthard, Huldrych F</au><au>Fellay, Jacques</au><au>Tarr, Philip E</au><aucorp>Swiss HIV Cohort Study</aucorp><aucorp>Swiss HIV Cohort Study</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Coronary Artery Disease–Associated and Longevity-Associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living With Human Immunodeficiency Virus: The Swiss HIV Cohort Study</atitle><jtitle>Clinical infectious diseases</jtitle><addtitle>Clin Infect Dis</addtitle><date>2021-11-02</date><risdate>2021</risdate><volume>73</volume><issue>9</issue><spage>1597</spage><epage>1604</epage><pages>1597-1604</pages><issn>1058-4838</issn><eissn>1537-6591</eissn><abstract>Abstract
Background
Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with human immunodeficiency virus (HIV) (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRSs) and by considering genetic variants associated with successful aging and longevity.
Methods
In the Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (ORs) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRSs. PRSs were built from CAD-associated single-nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both.
Results
We included 269 patients with CAD events between 2000 and 2017 (median age, 54 years; 87% male; 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (ie, traditional and HIV-related) risk factors and PRSs, built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (P < .001). Participants with the most unfavorable clinical risk factor profile (top quintile) had an adjusted CAD-OR of 17.82 (95% confidence interval [CI], 8.19–38.76), compared with participants in the bottom quintile. Participants with the most unfavorable CAD-PRSs (top quintile) had an adjusted CAD-OR of 3.17 (95% CI, 1.74–5.79), compared with the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had an adjusted CAD-OR of 3.67 (95% CI, 2.00–6.73), compared with the bottom quintile.
Conclusions
In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related, and genetic risk factors provided the most powerful CAD prediction.
Genetic background is associated with coronary artery disease (CAD) events. People living with human immunodeficiency virus have accentuated aging. Adding longevity-associated genetic variants to an individual polygenic risk score based on CAD-associated variants improves prediction of CAD events.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>34091660</pmid><doi>10.1093/cid/ciab521</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-2312-7050</orcidid><orcidid>https://orcid.org/0000-0003-0933-7833</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical infectious diseases, 2021-11, Vol.73 (9), p.1597-1604 |
| issn | 1058-4838 1537-6591 |
| language | eng |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Cohort Studies Coronary Artery Disease - epidemiology Coronary Artery Disease - genetics Female Genetic Predisposition to Disease HIV HIV Infections - complications HIV Infections - epidemiology Humans Longevity - genetics Male Middle Aged Polymorphism, Single Nucleotide Risk Factors Switzerland - epidemiology |
| title | Coronary Artery Disease–Associated and Longevity-Associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living With Human Immunodeficiency Virus: The Swiss HIV Cohort Study |
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