Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging
Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits—healthspan, father and mother lifespan...
Gespeichert in:
| Veröffentlicht in: | Nature aging 2022-01, Vol.2 (1), p.19-30 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 30 |
|---|---|
| container_issue | 1 |
| container_start_page | 19 |
| container_title | Nature aging |
| container_volume | 2 |
| creator | Timmers, Paul R. H. J. Tiys, Evgeny S. Sakaue, Saori Akiyama, Masato Kiiskinen, Tuomo T. J. Zhou, Wei Hwang, Shih-Jen Yao, Chen Deelen, Joris Levy, Daniel Ganna, Andrea Kamatani, Yoichiro Okada, Yukinori Joshi, Peter K. Wilson, James F. Tsepilov, Yakov A. |
| description | Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits—healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health—in a principal component framework that maximizes their shared genetic architecture. The first principal component (aging-GIP1) captures both length of life and indices of mental and physical wellbeing. We identify 27 genomic regions associated with aging-GIP1, and provide additional, independent evidence for an effect on human aging for loci near
HTT
and
MAML3
using a study of Finnish and Japanese survival. Using proteome-wide, two-sample, Mendelian randomization and colocalization, we provide robust evidence for a detrimental effect of blood levels of apolipoprotein(a) and vascular cell adhesion molecule 1 on aging-GIP1. Together, our results demonstrate that combining multiple aging traits using genetic principal components enhances the power to detect biological targets for human aging.
Many aging-related phenotypes share a common genetic component, but to disentangle disease-specific variants from aging-specific ones has been challenging. Here Timmers et al. combined several genetics studies of aging-related traits to identify common underlying genetic factors that contribute to aging. |
| doi_str_mv | 10.1038/s43587-021-00159-8 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2807915498</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3102044311</sourcerecordid><originalsourceid>FETCH-LOGICAL-c419t-a115d10d045d4ffeea7f5c8640bfc8a649397c76f4e0dab6f9c979bf620ef2223</originalsourceid><addsrcrecordid>eNp9kU1v1DAQhi0EolXpH-CALHHhEvBXHPu4WgGttBUcgKvlJOPUVWIHOzlsj_xynG75EAdOHnmeeWakF6GXlLylhKt3WfBaNRVhtCKE1rpST9A5k5JVSsj66V_1GbrM-Y4QwmrKiWTP0RlvKFVcsnP04wZCD6O3AScb-jj5e7v4GHB0eIAAi-_sOB6xL9S8oWHBdvBhwPMthLgcZ8jYb9_e-VIePu9w8eBv-90NxTbj1scxDpsFLzYNsGTsYsK361RWPpheoGfOjhkuH98L9PXD-y_7q-rw6eP1fneoOkH1UllK656Snoi6F84B2MbVnZKCtK5TVgrNddM10gkgvW2l051udOskI-AYY_wCvTl55xS_r5AXM_ncwTjaAHHNhinSaFoLrQr6-h_0Lq4plOsMp4QRITilhWInqksx5wTOzMlPNh0NJWYLyZxCMiUk8xCS2dSvHtVrO0H_e-RXJAXgJyCXVhgg_dn9H-1P-DWd3g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3102044311</pqid></control><display><type>article</type><title>Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Timmers, Paul R. H. J. ; Tiys, Evgeny S. ; Sakaue, Saori ; Akiyama, Masato ; Kiiskinen, Tuomo T. J. ; Zhou, Wei ; Hwang, Shih-Jen ; Yao, Chen ; Deelen, Joris ; Levy, Daniel ; Ganna, Andrea ; Kamatani, Yoichiro ; Okada, Yukinori ; Joshi, Peter K. ; Wilson, James F. ; Tsepilov, Yakov A.</creator><creatorcontrib>Timmers, Paul R. H. J. ; Tiys, Evgeny S. ; Sakaue, Saori ; Akiyama, Masato ; Kiiskinen, Tuomo T. J. ; Zhou, Wei ; Hwang, Shih-Jen ; Yao, Chen ; Deelen, Joris ; Levy, Daniel ; Ganna, Andrea ; Kamatani, Yoichiro ; Okada, Yukinori ; Joshi, Peter K. ; Wilson, James F. ; Tsepilov, Yakov A. ; Biobank Japan Project ; FinnGen ; Biobank Japan Project ; FinnGen</creatorcontrib><description>Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits—healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health—in a principal component framework that maximizes their shared genetic architecture. The first principal component (aging-GIP1) captures both length of life and indices of mental and physical wellbeing. We identify 27 genomic regions associated with aging-GIP1, and provide additional, independent evidence for an effect on human aging for loci near
HTT
and
MAML3
using a study of Finnish and Japanese survival. Using proteome-wide, two-sample, Mendelian randomization and colocalization, we provide robust evidence for a detrimental effect of blood levels of apolipoprotein(a) and vascular cell adhesion molecule 1 on aging-GIP1. Together, our results demonstrate that combining multiple aging traits using genetic principal components enhances the power to detect biological targets for human aging.
Many aging-related phenotypes share a common genetic component, but to disentangle disease-specific variants from aging-specific ones has been challenging. Here Timmers et al. combined several genetics studies of aging-related traits to identify common underlying genetic factors that contribute to aging.</description><identifier>ISSN: 2662-8465</identifier><identifier>EISSN: 2662-8465</identifier><identifier>DOI: 10.1038/s43587-021-00159-8</identifier><identifier>PMID: 37118362</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>45/43 ; 631/208/205/2138 ; 631/208/480 ; 631/443/7 ; Aging ; Aging - genetics ; Biomedical and Life Sciences ; Female ; Genome-Wide Association Study - methods ; Humans ; Life Sciences ; Mendelian Randomization Analysis ; Phenotype ; Quality of Life</subject><ispartof>Nature aging, 2022-01, Vol.2 (1), p.19-30</ispartof><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2022</rights><rights>2022. The Author(s), under exclusive licence to Springer Nature America, Inc.</rights><rights>The Author(s), under exclusive licence to Springer Nature America, Inc. 2022.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-a115d10d045d4ffeea7f5c8640bfc8a649397c76f4e0dab6f9c979bf620ef2223</citedby><cites>FETCH-LOGICAL-c419t-a115d10d045d4ffeea7f5c8640bfc8a649397c76f4e0dab6f9c979bf620ef2223</cites><orcidid>0000-0002-5197-1267 ; 0000-0001-5751-9178 ; 0000-0002-0311-8472 ; 0000-0003-3618-9717 ; 0000-0003-4483-3701 ; 0000-0002-4931-6052 ; 0000-0002-6306-8227</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37118362$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Timmers, Paul R. H. J.</creatorcontrib><creatorcontrib>Tiys, Evgeny S.</creatorcontrib><creatorcontrib>Sakaue, Saori</creatorcontrib><creatorcontrib>Akiyama, Masato</creatorcontrib><creatorcontrib>Kiiskinen, Tuomo T. J.</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Hwang, Shih-Jen</creatorcontrib><creatorcontrib>Yao, Chen</creatorcontrib><creatorcontrib>Deelen, Joris</creatorcontrib><creatorcontrib>Levy, Daniel</creatorcontrib><creatorcontrib>Ganna, Andrea</creatorcontrib><creatorcontrib>Kamatani, Yoichiro</creatorcontrib><creatorcontrib>Okada, Yukinori</creatorcontrib><creatorcontrib>Joshi, Peter K.</creatorcontrib><creatorcontrib>Wilson, James F.</creatorcontrib><creatorcontrib>Tsepilov, Yakov A.</creatorcontrib><creatorcontrib>Biobank Japan Project</creatorcontrib><creatorcontrib>FinnGen</creatorcontrib><creatorcontrib>Biobank Japan Project</creatorcontrib><creatorcontrib>FinnGen</creatorcontrib><title>Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging</title><title>Nature aging</title><addtitle>Nat Aging</addtitle><addtitle>Nat Aging</addtitle><description>Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits—healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health—in a principal component framework that maximizes their shared genetic architecture. The first principal component (aging-GIP1) captures both length of life and indices of mental and physical wellbeing. We identify 27 genomic regions associated with aging-GIP1, and provide additional, independent evidence for an effect on human aging for loci near
HTT
and
MAML3
using a study of Finnish and Japanese survival. Using proteome-wide, two-sample, Mendelian randomization and colocalization, we provide robust evidence for a detrimental effect of blood levels of apolipoprotein(a) and vascular cell adhesion molecule 1 on aging-GIP1. Together, our results demonstrate that combining multiple aging traits using genetic principal components enhances the power to detect biological targets for human aging.
Many aging-related phenotypes share a common genetic component, but to disentangle disease-specific variants from aging-specific ones has been challenging. Here Timmers et al. combined several genetics studies of aging-related traits to identify common underlying genetic factors that contribute to aging.</description><subject>45/43</subject><subject>631/208/205/2138</subject><subject>631/208/480</subject><subject>631/443/7</subject><subject>Aging</subject><subject>Aging - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Female</subject><subject>Genome-Wide Association Study - methods</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Mendelian Randomization Analysis</subject><subject>Phenotype</subject><subject>Quality of Life</subject><issn>2662-8465</issn><issn>2662-8465</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kU1v1DAQhi0EolXpH-CALHHhEvBXHPu4WgGttBUcgKvlJOPUVWIHOzlsj_xynG75EAdOHnmeeWakF6GXlLylhKt3WfBaNRVhtCKE1rpST9A5k5JVSsj66V_1GbrM-Y4QwmrKiWTP0RlvKFVcsnP04wZCD6O3AScb-jj5e7v4GHB0eIAAi-_sOB6xL9S8oWHBdvBhwPMthLgcZ8jYb9_e-VIePu9w8eBv-90NxTbj1scxDpsFLzYNsGTsYsK361RWPpheoGfOjhkuH98L9PXD-y_7q-rw6eP1fneoOkH1UllK656Snoi6F84B2MbVnZKCtK5TVgrNddM10gkgvW2l051udOskI-AYY_wCvTl55xS_r5AXM_ncwTjaAHHNhinSaFoLrQr6-h_0Lq4plOsMp4QRITilhWInqksx5wTOzMlPNh0NJWYLyZxCMiUk8xCS2dSvHtVrO0H_e-RXJAXgJyCXVhgg_dn9H-1P-DWd3g</recordid><startdate>20220101</startdate><enddate>20220101</enddate><creator>Timmers, Paul R. H. J.</creator><creator>Tiys, Evgeny S.</creator><creator>Sakaue, Saori</creator><creator>Akiyama, Masato</creator><creator>Kiiskinen, Tuomo T. J.</creator><creator>Zhou, Wei</creator><creator>Hwang, Shih-Jen</creator><creator>Yao, Chen</creator><creator>Deelen, Joris</creator><creator>Levy, Daniel</creator><creator>Ganna, Andrea</creator><creator>Kamatani, Yoichiro</creator><creator>Okada, Yukinori</creator><creator>Joshi, Peter K.</creator><creator>Wilson, James F.</creator><creator>Tsepilov, Yakov A.</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5197-1267</orcidid><orcidid>https://orcid.org/0000-0001-5751-9178</orcidid><orcidid>https://orcid.org/0000-0002-0311-8472</orcidid><orcidid>https://orcid.org/0000-0003-3618-9717</orcidid><orcidid>https://orcid.org/0000-0003-4483-3701</orcidid><orcidid>https://orcid.org/0000-0002-4931-6052</orcidid><orcidid>https://orcid.org/0000-0002-6306-8227</orcidid></search><sort><creationdate>20220101</creationdate><title>Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging</title><author>Timmers, Paul R. H. J. ; Tiys, Evgeny S. ; Sakaue, Saori ; Akiyama, Masato ; Kiiskinen, Tuomo T. J. ; Zhou, Wei ; Hwang, Shih-Jen ; Yao, Chen ; Deelen, Joris ; Levy, Daniel ; Ganna, Andrea ; Kamatani, Yoichiro ; Okada, Yukinori ; Joshi, Peter K. ; Wilson, James F. ; Tsepilov, Yakov A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-a115d10d045d4ffeea7f5c8640bfc8a649397c76f4e0dab6f9c979bf620ef2223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>45/43</topic><topic>631/208/205/2138</topic><topic>631/208/480</topic><topic>631/443/7</topic><topic>Aging</topic><topic>Aging - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Female</topic><topic>Genome-Wide Association Study - methods</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Mendelian Randomization Analysis</topic><topic>Phenotype</topic><topic>Quality of Life</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Timmers, Paul R. H. J.</creatorcontrib><creatorcontrib>Tiys, Evgeny S.</creatorcontrib><creatorcontrib>Sakaue, Saori</creatorcontrib><creatorcontrib>Akiyama, Masato</creatorcontrib><creatorcontrib>Kiiskinen, Tuomo T. J.</creatorcontrib><creatorcontrib>Zhou, Wei</creatorcontrib><creatorcontrib>Hwang, Shih-Jen</creatorcontrib><creatorcontrib>Yao, Chen</creatorcontrib><creatorcontrib>Deelen, Joris</creatorcontrib><creatorcontrib>Levy, Daniel</creatorcontrib><creatorcontrib>Ganna, Andrea</creatorcontrib><creatorcontrib>Kamatani, Yoichiro</creatorcontrib><creatorcontrib>Okada, Yukinori</creatorcontrib><creatorcontrib>Joshi, Peter K.</creatorcontrib><creatorcontrib>Wilson, James F.</creatorcontrib><creatorcontrib>Tsepilov, Yakov A.</creatorcontrib><creatorcontrib>Biobank Japan Project</creatorcontrib><creatorcontrib>FinnGen</creatorcontrib><creatorcontrib>Biobank Japan Project</creatorcontrib><creatorcontrib>FinnGen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Nature aging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Timmers, Paul R. H. J.</au><au>Tiys, Evgeny S.</au><au>Sakaue, Saori</au><au>Akiyama, Masato</au><au>Kiiskinen, Tuomo T. J.</au><au>Zhou, Wei</au><au>Hwang, Shih-Jen</au><au>Yao, Chen</au><au>Deelen, Joris</au><au>Levy, Daniel</au><au>Ganna, Andrea</au><au>Kamatani, Yoichiro</au><au>Okada, Yukinori</au><au>Joshi, Peter K.</au><au>Wilson, James F.</au><au>Tsepilov, Yakov A.</au><aucorp>Biobank Japan Project</aucorp><aucorp>FinnGen</aucorp><aucorp>Biobank Japan Project</aucorp><aucorp>FinnGen</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging</atitle><jtitle>Nature aging</jtitle><stitle>Nat Aging</stitle><addtitle>Nat Aging</addtitle><date>2022-01-01</date><risdate>2022</risdate><volume>2</volume><issue>1</issue><spage>19</spage><epage>30</epage><pages>19-30</pages><issn>2662-8465</issn><eissn>2662-8465</eissn><abstract>Length and quality of life are important to us all, yet identification of promising drug targets for human aging using genetics has had limited success. In the present study, we combine six European-ancestry genome-wide association studies of human aging traits—healthspan, father and mother lifespan, exceptional longevity, frailty index and self-rated health—in a principal component framework that maximizes their shared genetic architecture. The first principal component (aging-GIP1) captures both length of life and indices of mental and physical wellbeing. We identify 27 genomic regions associated with aging-GIP1, and provide additional, independent evidence for an effect on human aging for loci near
HTT
and
MAML3
using a study of Finnish and Japanese survival. Using proteome-wide, two-sample, Mendelian randomization and colocalization, we provide robust evidence for a detrimental effect of blood levels of apolipoprotein(a) and vascular cell adhesion molecule 1 on aging-GIP1. Together, our results demonstrate that combining multiple aging traits using genetic principal components enhances the power to detect biological targets for human aging.
Many aging-related phenotypes share a common genetic component, but to disentangle disease-specific variants from aging-specific ones has been challenging. Here Timmers et al. combined several genetics studies of aging-related traits to identify common underlying genetic factors that contribute to aging.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>37118362</pmid><doi>10.1038/s43587-021-00159-8</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-5197-1267</orcidid><orcidid>https://orcid.org/0000-0001-5751-9178</orcidid><orcidid>https://orcid.org/0000-0002-0311-8472</orcidid><orcidid>https://orcid.org/0000-0003-3618-9717</orcidid><orcidid>https://orcid.org/0000-0003-4483-3701</orcidid><orcidid>https://orcid.org/0000-0002-4931-6052</orcidid><orcidid>https://orcid.org/0000-0002-6306-8227</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2662-8465 |
| ispartof | Nature aging, 2022-01, Vol.2 (1), p.19-30 |
| issn | 2662-8465 2662-8465 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2807915498 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | 45/43 631/208/205/2138 631/208/480 631/443/7 Aging Aging - genetics Biomedical and Life Sciences Female Genome-Wide Association Study - methods Humans Life Sciences Mendelian Randomization Analysis Phenotype Quality of Life |
| title | Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T22%3A23%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Mendelian%20randomization%20of%20genetically%20independent%20aging%20phenotypes%20identifies%20LPA%20and%20VCAM1%20as%20biological%20targets%20for%20human%20aging&rft.jtitle=Nature%20aging&rft.au=Timmers,%20Paul%20R.%20H.%20J.&rft.aucorp=Biobank%20Japan%20Project&rft.date=2022-01-01&rft.volume=2&rft.issue=1&rft.spage=19&rft.epage=30&rft.pages=19-30&rft.issn=2662-8465&rft.eissn=2662-8465&rft_id=info:doi/10.1038/s43587-021-00159-8&rft_dat=%3Cproquest_cross%3E3102044311%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3102044311&rft_id=info:pmid/37118362&rfr_iscdi=true |