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Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis
Background The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angl...
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| Published in: | Eye (London) 2024-12, Vol.38 (17), p.3347-3351 |
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| creator | Katsimpris, Andreas Baumeister, Sebastian-Edgar Voulgari, Nafsika Baurecht, Hansjörg Kandarakis, Stylianos Nolde, Michael |
| description | Background
The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angle glaucoma (POAG), or if it arises as a consequence of the sequelae of POAG. Therefore, we conducted a Mendelian Randomization (MR) mediation analysis to elucidate the mediating role of POAG in the association between IOP and RVO.
Methods
We identified 47 single-nucleotide polymorphisms (SNPs) associated with IOP (
P
-value |
| doi_str_mv | 10.1038/s41433-024-03303-x |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11584727</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3093594355</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-976d44b07d0b1cbca6bfc21178887f68f34674e0176c9f5ea8c34dff2b36f7b03</originalsourceid><addsrcrecordid>eNp9Uc1uFSEYJcbG3l59AReGxI2LjsIAw4ybpmn8aVLjRhN3hGE-bqkMXGGmaX2APnepc23VhStOcn74Tg5Czyl5TQlr32ROOWMVqXlFGCOsunqEVpTLphJc8MdoRTpBqrquv-2jg5wvCCmkJE_QPusKahuxQjenYUo6mtnrhLcJcp4THBbkRp2ucdxCqHTYeMAbr2cTR411GPB0Dji5_B1HixNMLmiPL8EFHI3xc3YxvMXH-BOEAbzTAadiiqP7qadC4REGtyBdjNfZ5adoz2qf4dnuXaOv7999OflYnX3-cHpyfFYZJpqp6mQzcN4TOZCemt7opremplS2bStt01rGG8mBUNmYzgrQrWF8sLbuWWNlT9gaHS2527kvVxi4a-_Vrq6K2qm_meDO1SZeKkpFy2UtS8KrXUKKP2bIkxpdNuC9DhDnrBjpmOg4E6JIX_4jvYhzKo2LirKa0I6X3daoXlQmxZwT2PtrKFF3O6tlZ1V2Vr92VlfF9OLPHveW38MWAVsEuVBhA-nh7__E3gJIGrd-</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3132019403</pqid></control><display><type>article</type><title>Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis</title><source>Springer Nature</source><creator>Katsimpris, Andreas ; Baumeister, Sebastian-Edgar ; Voulgari, Nafsika ; Baurecht, Hansjörg ; Kandarakis, Stylianos ; Nolde, Michael</creator><creatorcontrib>Katsimpris, Andreas ; Baumeister, Sebastian-Edgar ; Voulgari, Nafsika ; Baurecht, Hansjörg ; Kandarakis, Stylianos ; Nolde, Michael</creatorcontrib><description>Background
The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angle glaucoma (POAG), or if it arises as a consequence of the sequelae of POAG. Therefore, we conducted a Mendelian Randomization (MR) mediation analysis to elucidate the mediating role of POAG in the association between IOP and RVO.
Methods
We identified 47 single-nucleotide polymorphisms (SNPs) associated with IOP (
P
-value < 5 × 10
−8
) leveraging data from a genome-wide association study (GWAS) (
N
= 97,653) obtained from the UK Biobank and 50 SNPs associated with POAG (
P
-value < 5 × 10
−8
) from a GWAS meta-analysis (16,677 cases and 199,580 controls). We related these SNPs with RVO using a GWAS of 775 RVO cases and 376,502 controls from FinnGen. By utilizing univariable and multivariable MR analyses we calculated the total effect of IOP on RVO and estimated the degree to which POAG mediates this association.
Results
MR analyses showed that higher IOP is associated with higher RVO risk (odds ratio of RVO per 1 mmHg increase in IOP: 1.53; 95% confidence interval: 1.04 to 2.26;
p
-value = 0.03). Moreover, our MR mediation analysis suggested that 91.6% of the total effect of IOP on RVO risk was mediated through POAG. The primary results were consistent with estimates of pleiotropy-robust MR methods.
Conclusion
Our findings suggest that higher IOP increases the risk of RVO and that the majority of this effect is mediated through POAG.</description><identifier>ISSN: 0950-222X</identifier><identifier>ISSN: 1476-5454</identifier><identifier>EISSN: 1476-5454</identifier><identifier>DOI: 10.1038/s41433-024-03303-x</identifier><identifier>PMID: 39147865</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/23 ; 692/499 ; 692/699/3161/3175 ; Aged ; Complications ; Female ; Genetic Predisposition to Disease ; Genome-wide association studies ; Genome-Wide Association Study ; Glaucoma ; Glaucoma, Open-Angle - genetics ; Humans ; Intraocular Pressure - physiology ; Laboratory Medicine ; Male ; Mediation Analysis ; Medicine ; Medicine & Public Health ; Mendelian Randomization Analysis ; Middle Aged ; Occlusion ; Ophthalmology ; Pharmaceutical Sciences/Technology ; Pleiotropy ; Polymorphism, Single Nucleotide ; Retina ; Retinal Vein Occlusion - epidemiology ; Retinal Vein Occlusion - genetics ; Risk Factors ; Single-nucleotide polymorphism ; Surgery ; Surgical Oncology ; United Kingdom - epidemiology</subject><ispartof>Eye (London), 2024-12, Vol.38 (17), p.3347-3351</ispartof><rights>The Author(s) 2024. corrected publication 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. corrected publication 2024. 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>The Author(s) 2024, corrected publication 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c356t-976d44b07d0b1cbca6bfc21178887f68f34674e0176c9f5ea8c34dff2b36f7b03</cites><orcidid>0000-0002-5805-105X ; 0000-0003-2912-7438</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39147865$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Katsimpris, Andreas</creatorcontrib><creatorcontrib>Baumeister, Sebastian-Edgar</creatorcontrib><creatorcontrib>Voulgari, Nafsika</creatorcontrib><creatorcontrib>Baurecht, Hansjörg</creatorcontrib><creatorcontrib>Kandarakis, Stylianos</creatorcontrib><creatorcontrib>Nolde, Michael</creatorcontrib><title>Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis</title><title>Eye (London)</title><addtitle>Eye</addtitle><addtitle>Eye (Lond)</addtitle><description>Background
The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angle glaucoma (POAG), or if it arises as a consequence of the sequelae of POAG. Therefore, we conducted a Mendelian Randomization (MR) mediation analysis to elucidate the mediating role of POAG in the association between IOP and RVO.
Methods
We identified 47 single-nucleotide polymorphisms (SNPs) associated with IOP (
P
-value < 5 × 10
−8
) leveraging data from a genome-wide association study (GWAS) (
N
= 97,653) obtained from the UK Biobank and 50 SNPs associated with POAG (
P
-value < 5 × 10
−8
) from a GWAS meta-analysis (16,677 cases and 199,580 controls). We related these SNPs with RVO using a GWAS of 775 RVO cases and 376,502 controls from FinnGen. By utilizing univariable and multivariable MR analyses we calculated the total effect of IOP on RVO and estimated the degree to which POAG mediates this association.
Results
MR analyses showed that higher IOP is associated with higher RVO risk (odds ratio of RVO per 1 mmHg increase in IOP: 1.53; 95% confidence interval: 1.04 to 2.26;
p
-value = 0.03). Moreover, our MR mediation analysis suggested that 91.6% of the total effect of IOP on RVO risk was mediated through POAG. The primary results were consistent with estimates of pleiotropy-robust MR methods.
Conclusion
Our findings suggest that higher IOP increases the risk of RVO and that the majority of this effect is mediated through POAG.</description><subject>38/23</subject><subject>692/499</subject><subject>692/699/3161/3175</subject><subject>Aged</subject><subject>Complications</subject><subject>Female</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Glaucoma</subject><subject>Glaucoma, Open-Angle - genetics</subject><subject>Humans</subject><subject>Intraocular Pressure - physiology</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Mediation Analysis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mendelian Randomization Analysis</subject><subject>Middle Aged</subject><subject>Occlusion</subject><subject>Ophthalmology</subject><subject>Pharmaceutical Sciences/Technology</subject><subject>Pleiotropy</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Retina</subject><subject>Retinal Vein Occlusion - epidemiology</subject><subject>Retinal Vein Occlusion - genetics</subject><subject>Risk Factors</subject><subject>Single-nucleotide polymorphism</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>United Kingdom - epidemiology</subject><issn>0950-222X</issn><issn>1476-5454</issn><issn>1476-5454</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9Uc1uFSEYJcbG3l59AReGxI2LjsIAw4ybpmn8aVLjRhN3hGE-bqkMXGGmaX2APnepc23VhStOcn74Tg5Czyl5TQlr32ROOWMVqXlFGCOsunqEVpTLphJc8MdoRTpBqrquv-2jg5wvCCmkJE_QPusKahuxQjenYUo6mtnrhLcJcp4THBbkRp2ucdxCqHTYeMAbr2cTR411GPB0Dji5_B1HixNMLmiPL8EFHI3xc3YxvMXH-BOEAbzTAadiiqP7qadC4REGtyBdjNfZ5adoz2qf4dnuXaOv7999OflYnX3-cHpyfFYZJpqp6mQzcN4TOZCemt7opremplS2bStt01rGG8mBUNmYzgrQrWF8sLbuWWNlT9gaHS2527kvVxi4a-_Vrq6K2qm_meDO1SZeKkpFy2UtS8KrXUKKP2bIkxpdNuC9DhDnrBjpmOg4E6JIX_4jvYhzKo2LirKa0I6X3daoXlQmxZwT2PtrKFF3O6tlZ1V2Vr92VlfF9OLPHveW38MWAVsEuVBhA-nh7__E3gJIGrd-</recordid><startdate>202412</startdate><enddate>202412</enddate><creator>Katsimpris, Andreas</creator><creator>Baumeister, Sebastian-Edgar</creator><creator>Voulgari, Nafsika</creator><creator>Baurecht, Hansjörg</creator><creator>Kandarakis, Stylianos</creator><creator>Nolde, Michael</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><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>7TK</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5805-105X</orcidid><orcidid>https://orcid.org/0000-0003-2912-7438</orcidid></search><sort><creationdate>202412</creationdate><title>Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis</title><author>Katsimpris, Andreas ; Baumeister, Sebastian-Edgar ; Voulgari, Nafsika ; Baurecht, Hansjörg ; Kandarakis, Stylianos ; Nolde, Michael</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-976d44b07d0b1cbca6bfc21178887f68f34674e0176c9f5ea8c34dff2b36f7b03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>38/23</topic><topic>692/499</topic><topic>692/699/3161/3175</topic><topic>Aged</topic><topic>Complications</topic><topic>Female</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Glaucoma</topic><topic>Glaucoma, Open-Angle - genetics</topic><topic>Humans</topic><topic>Intraocular Pressure - physiology</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Mediation Analysis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mendelian Randomization Analysis</topic><topic>Middle Aged</topic><topic>Occlusion</topic><topic>Ophthalmology</topic><topic>Pharmaceutical Sciences/Technology</topic><topic>Pleiotropy</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Retina</topic><topic>Retinal Vein Occlusion - epidemiology</topic><topic>Retinal Vein Occlusion - genetics</topic><topic>Risk Factors</topic><topic>Single-nucleotide polymorphism</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>United Kingdom - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Katsimpris, Andreas</creatorcontrib><creatorcontrib>Baumeister, Sebastian-Edgar</creatorcontrib><creatorcontrib>Voulgari, Nafsika</creatorcontrib><creatorcontrib>Baurecht, Hansjörg</creatorcontrib><creatorcontrib>Kandarakis, Stylianos</creatorcontrib><creatorcontrib>Nolde, Michael</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Eye (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Katsimpris, Andreas</au><au>Baumeister, Sebastian-Edgar</au><au>Voulgari, Nafsika</au><au>Baurecht, Hansjörg</au><au>Kandarakis, Stylianos</au><au>Nolde, Michael</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis</atitle><jtitle>Eye (London)</jtitle><stitle>Eye</stitle><addtitle>Eye (Lond)</addtitle><date>2024-12</date><risdate>2024</risdate><volume>38</volume><issue>17</issue><spage>3347</spage><epage>3351</epage><pages>3347-3351</pages><issn>0950-222X</issn><issn>1476-5454</issn><eissn>1476-5454</eissn><abstract>Background
The etiological connection between intraocular pressure (IOP) and the risk of retinal vein occlusion (RVO) remains elusive, particularly regarding whether this risk emanates from the direct influence of elevated intraocular pressure (IOP), irrespective of the presence of primary open-angle glaucoma (POAG), or if it arises as a consequence of the sequelae of POAG. Therefore, we conducted a Mendelian Randomization (MR) mediation analysis to elucidate the mediating role of POAG in the association between IOP and RVO.
Methods
We identified 47 single-nucleotide polymorphisms (SNPs) associated with IOP (
P
-value < 5 × 10
−8
) leveraging data from a genome-wide association study (GWAS) (
N
= 97,653) obtained from the UK Biobank and 50 SNPs associated with POAG (
P
-value < 5 × 10
−8
) from a GWAS meta-analysis (16,677 cases and 199,580 controls). We related these SNPs with RVO using a GWAS of 775 RVO cases and 376,502 controls from FinnGen. By utilizing univariable and multivariable MR analyses we calculated the total effect of IOP on RVO and estimated the degree to which POAG mediates this association.
Results
MR analyses showed that higher IOP is associated with higher RVO risk (odds ratio of RVO per 1 mmHg increase in IOP: 1.53; 95% confidence interval: 1.04 to 2.26;
p
-value = 0.03). Moreover, our MR mediation analysis suggested that 91.6% of the total effect of IOP on RVO risk was mediated through POAG. The primary results were consistent with estimates of pleiotropy-robust MR methods.
Conclusion
Our findings suggest that higher IOP increases the risk of RVO and that the majority of this effect is mediated through POAG.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>39147865</pmid><doi>10.1038/s41433-024-03303-x</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-5805-105X</orcidid><orcidid>https://orcid.org/0000-0003-2912-7438</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Springer Nature |
| subjects | 38/23 692/499 692/699/3161/3175 Aged Complications Female Genetic Predisposition to Disease Genome-wide association studies Genome-Wide Association Study Glaucoma Glaucoma, Open-Angle - genetics Humans Intraocular Pressure - physiology Laboratory Medicine Male Mediation Analysis Medicine Medicine & Public Health Mendelian Randomization Analysis Middle Aged Occlusion Ophthalmology Pharmaceutical Sciences/Technology Pleiotropy Polymorphism, Single Nucleotide Retina Retinal Vein Occlusion - epidemiology Retinal Vein Occlusion - genetics Risk Factors Single-nucleotide polymorphism Surgery Surgical Oncology United Kingdom - epidemiology |
| title | Intraocular pressure, primary open-angle glaucoma and the risk of retinal vein occlusion: A Mendelian randomization mediation analysis |
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