Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration
Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and...
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| Veröffentlicht in: | Cell reports. Medicine 2023-07, Vol.4 (7), p.101085-101085, Article 101085 |
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| creator | Han, Xikun Lains, Ines Li, Jun Li, Jinglun Chen, Yiheng Yu, Bing Qi, Qibin Boerwinkle, Eric Kaplan, Robert Thyagarajan, Bharat Daviglus, Martha Joslin, Charlotte E. Cai, Jianwen Guasch-Ferré, Marta Tobias, Deirdre K. Rimm, Eric Ascherio, Alberto Costenbader, Karen Karlson, Elizabeth Mucci, Lorelei Eliassen, A. Heather Zeleznik, Oana Miller, John Vavvas, Demetrios G. Kim, Ivana K. Silva, Rufino Miller, Joan Hu, Frank Willett, Walter Lasky-Su, Jessica Kraft, Peter Richards, J. Brent MacGregor, Stuart Husain, Deeba Liang, Liming |
| description | Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.
[Display omitted]
•Large-scale metabolite genome-wide association studies identify mQTLs in plasma and urine•Two-sample Mendelian randomization analysis uncovers 108 plasma metabolites associated with AMD•AMD-associated metabolites are enriched in lipid-related pathways•Systematic exploration of metabolite connections with AMD subtypes and lipid biomarkers
In this study, Han et al. conduct large-scale integrative genetic and metabolomic analysis and discover 108 plasma metabolites associated with advanced age-related macular degeneration. The identified metabolites are enriched in pathways of glycerophospholipid metabolism, lysophospholipid, triradylcglycerols, and long-chain polyunsaturated fatty acids, providing insight into their potential in AMD pathogenesis. |
| doi_str_mv | 10.1016/j.xcrm.2023.101085 |
| format | Article |
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[Display omitted]
•Large-scale metabolite genome-wide association studies identify mQTLs in plasma and urine•Two-sample Mendelian randomization analysis uncovers 108 plasma metabolites associated with AMD•AMD-associated metabolites are enriched in lipid-related pathways•Systematic exploration of metabolite connections with AMD subtypes and lipid biomarkers
In this study, Han et al. conduct large-scale integrative genetic and metabolomic analysis and discover 108 plasma metabolites associated with advanced age-related macular degeneration. The identified metabolites are enriched in pathways of glycerophospholipid metabolism, lysophospholipid, triradylcglycerols, and long-chain polyunsaturated fatty acids, providing insight into their potential in AMD pathogenesis.</description><identifier>ISSN: 2666-3791</identifier><identifier>EISSN: 2666-3791</identifier><identifier>DOI: 10.1016/j.xcrm.2023.101085</identifier><identifier>PMID: 37348500</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>age-related macular degeneration ; Aged ; AMD ; Bayes Theorem ; Canadian Longitudinal Study of Aging ; CLSA ; genome-wide association studies ; Genome-Wide Association Study ; genomics ; GWASs ; HCHS/SOL ; Health Professionals Follow Up Study ; Hispanic Community Health Study/Study of Latinos ; HPFS ; Humans ; Macular Degeneration - genetics ; Macular Degeneration - metabolism ; Mendelian randomization ; Metabolome - genetics ; Metabolomics ; NHS ; Nurses’ Health Study ; UK Biobank</subject><ispartof>Cell reports. Medicine, 2023-07, Vol.4 (7), p.101085-101085, Article 101085</ispartof><rights>2023 The Authors</rights><rights>Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2023 The Authors 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-bedc24d0cfc0e09d75af6d07a9735452fd2b760660e53705d8c45a72dd8fde683</citedby><cites>FETCH-LOGICAL-c456t-bedc24d0cfc0e09d75af6d07a9735452fd2b760660e53705d8c45a72dd8fde683</cites><orcidid>0000-0002-3823-7308</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/PMC10394104/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10394104/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37348500$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Han, Xikun</creatorcontrib><creatorcontrib>Lains, Ines</creatorcontrib><creatorcontrib>Li, Jun</creatorcontrib><creatorcontrib>Li, Jinglun</creatorcontrib><creatorcontrib>Chen, Yiheng</creatorcontrib><creatorcontrib>Yu, Bing</creatorcontrib><creatorcontrib>Qi, Qibin</creatorcontrib><creatorcontrib>Boerwinkle, Eric</creatorcontrib><creatorcontrib>Kaplan, Robert</creatorcontrib><creatorcontrib>Thyagarajan, Bharat</creatorcontrib><creatorcontrib>Daviglus, Martha</creatorcontrib><creatorcontrib>Joslin, Charlotte E.</creatorcontrib><creatorcontrib>Cai, Jianwen</creatorcontrib><creatorcontrib>Guasch-Ferré, Marta</creatorcontrib><creatorcontrib>Tobias, Deirdre K.</creatorcontrib><creatorcontrib>Rimm, Eric</creatorcontrib><creatorcontrib>Ascherio, Alberto</creatorcontrib><creatorcontrib>Costenbader, Karen</creatorcontrib><creatorcontrib>Karlson, Elizabeth</creatorcontrib><creatorcontrib>Mucci, Lorelei</creatorcontrib><creatorcontrib>Eliassen, A. Heather</creatorcontrib><creatorcontrib>Zeleznik, Oana</creatorcontrib><creatorcontrib>Miller, John</creatorcontrib><creatorcontrib>Vavvas, Demetrios G.</creatorcontrib><creatorcontrib>Kim, Ivana K.</creatorcontrib><creatorcontrib>Silva, Rufino</creatorcontrib><creatorcontrib>Miller, Joan</creatorcontrib><creatorcontrib>Hu, Frank</creatorcontrib><creatorcontrib>Willett, Walter</creatorcontrib><creatorcontrib>Lasky-Su, Jessica</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Richards, J. Brent</creatorcontrib><creatorcontrib>MacGregor, Stuart</creatorcontrib><creatorcontrib>Husain, Deeba</creatorcontrib><creatorcontrib>Liang, Liming</creatorcontrib><title>Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration</title><title>Cell reports. Medicine</title><addtitle>Cell Rep Med</addtitle><description>Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.
[Display omitted]
•Large-scale metabolite genome-wide association studies identify mQTLs in plasma and urine•Two-sample Mendelian randomization analysis uncovers 108 plasma metabolites associated with AMD•AMD-associated metabolites are enriched in lipid-related pathways•Systematic exploration of metabolite connections with AMD subtypes and lipid biomarkers
In this study, Han et al. conduct large-scale integrative genetic and metabolomic analysis and discover 108 plasma metabolites associated with advanced age-related macular degeneration. The identified metabolites are enriched in pathways of glycerophospholipid metabolism, lysophospholipid, triradylcglycerols, and long-chain polyunsaturated fatty acids, providing insight into their potential in AMD pathogenesis.</description><subject>age-related macular degeneration</subject><subject>Aged</subject><subject>AMD</subject><subject>Bayes Theorem</subject><subject>Canadian Longitudinal Study of Aging</subject><subject>CLSA</subject><subject>genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>genomics</subject><subject>GWASs</subject><subject>HCHS/SOL</subject><subject>Health Professionals Follow Up Study</subject><subject>Hispanic Community Health Study/Study of Latinos</subject><subject>HPFS</subject><subject>Humans</subject><subject>Macular Degeneration - genetics</subject><subject>Macular Degeneration - metabolism</subject><subject>Mendelian randomization</subject><subject>Metabolome - genetics</subject><subject>Metabolomics</subject><subject>NHS</subject><subject>Nurses’ Health Study</subject><subject>UK Biobank</subject><issn>2666-3791</issn><issn>2666-3791</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhSMEolXpC7BAWbLJcOMkTiIhIVTxU6kSG1hbd-ybjEf-GWxnBA_BO-OQUpUNK1vH53z3yqcoXtawq6Hmb467HzLYHQPWrAIM3ZPiknHOq6Yf66eP7hfFdYxHAGBdXQ8NPC8umr5phw7gsvh16xLNAZN2czmTo6RlLNGp0lLCvTfersIUvC3tYpKuKB2clpvljzCZRatSYcIy0JnQxPK0pEw8U4bIAzodbUb4UOJMVSCDiXIY5WIwlIrWsesG3r0onk05T9f351Xx7eOHrzefq7svn25v3t9Vsu14qvakJGsVyEkCwaj6DieuoMexb7q2Y5Ni-54D50Bd00OnhpzDnik1TIr40FwV7zbuadnbDCOXAhpxCtpi-Ck8avHvi9MHMfuzqKEZ2xraTHh9Twj--0IxCaujJGPQkV-iYAMbW8azPVvZZpXBxxhoephTg1i7FEexdinWLsXWZQ69erzhQ-Rvc9nwdjNQ_qezpiCi1OQkKR1IJqG8_h__N1udtNc</recordid><startdate>20230718</startdate><enddate>20230718</enddate><creator>Han, Xikun</creator><creator>Lains, Ines</creator><creator>Li, Jun</creator><creator>Li, Jinglun</creator><creator>Chen, Yiheng</creator><creator>Yu, Bing</creator><creator>Qi, Qibin</creator><creator>Boerwinkle, Eric</creator><creator>Kaplan, Robert</creator><creator>Thyagarajan, Bharat</creator><creator>Daviglus, Martha</creator><creator>Joslin, Charlotte E.</creator><creator>Cai, Jianwen</creator><creator>Guasch-Ferré, Marta</creator><creator>Tobias, Deirdre K.</creator><creator>Rimm, Eric</creator><creator>Ascherio, Alberto</creator><creator>Costenbader, Karen</creator><creator>Karlson, Elizabeth</creator><creator>Mucci, Lorelei</creator><creator>Eliassen, A. Heather</creator><creator>Zeleznik, Oana</creator><creator>Miller, John</creator><creator>Vavvas, Demetrios G.</creator><creator>Kim, Ivana K.</creator><creator>Silva, Rufino</creator><creator>Miller, Joan</creator><creator>Hu, Frank</creator><creator>Willett, Walter</creator><creator>Lasky-Su, Jessica</creator><creator>Kraft, Peter</creator><creator>Richards, J. Brent</creator><creator>MacGregor, Stuart</creator><creator>Husain, Deeba</creator><creator>Liang, Liming</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3823-7308</orcidid></search><sort><creationdate>20230718</creationdate><title>Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration</title><author>Han, Xikun ; Lains, Ines ; Li, Jun ; Li, Jinglun ; Chen, Yiheng ; Yu, Bing ; Qi, Qibin ; Boerwinkle, Eric ; Kaplan, Robert ; Thyagarajan, Bharat ; Daviglus, Martha ; Joslin, Charlotte E. ; Cai, Jianwen ; Guasch-Ferré, Marta ; Tobias, Deirdre K. ; Rimm, Eric ; Ascherio, Alberto ; Costenbader, Karen ; Karlson, Elizabeth ; Mucci, Lorelei ; Eliassen, A. Heather ; Zeleznik, Oana ; Miller, John ; Vavvas, Demetrios G. ; Kim, Ivana K. ; Silva, Rufino ; Miller, Joan ; Hu, Frank ; Willett, Walter ; Lasky-Su, Jessica ; Kraft, Peter ; Richards, J. 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Brent</creatorcontrib><creatorcontrib>MacGregor, Stuart</creatorcontrib><creatorcontrib>Husain, Deeba</creatorcontrib><creatorcontrib>Liang, Liming</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell reports. Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Han, Xikun</au><au>Lains, Ines</au><au>Li, Jun</au><au>Li, Jinglun</au><au>Chen, Yiheng</au><au>Yu, Bing</au><au>Qi, Qibin</au><au>Boerwinkle, Eric</au><au>Kaplan, Robert</au><au>Thyagarajan, Bharat</au><au>Daviglus, Martha</au><au>Joslin, Charlotte E.</au><au>Cai, Jianwen</au><au>Guasch-Ferré, Marta</au><au>Tobias, Deirdre K.</au><au>Rimm, Eric</au><au>Ascherio, Alberto</au><au>Costenbader, Karen</au><au>Karlson, Elizabeth</au><au>Mucci, Lorelei</au><au>Eliassen, A. Heather</au><au>Zeleznik, Oana</au><au>Miller, John</au><au>Vavvas, Demetrios G.</au><au>Kim, Ivana K.</au><au>Silva, Rufino</au><au>Miller, Joan</au><au>Hu, Frank</au><au>Willett, Walter</au><au>Lasky-Su, Jessica</au><au>Kraft, Peter</au><au>Richards, J. Brent</au><au>MacGregor, Stuart</au><au>Husain, Deeba</au><au>Liang, Liming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration</atitle><jtitle>Cell reports. Medicine</jtitle><addtitle>Cell Rep Med</addtitle><date>2023-07-18</date><risdate>2023</risdate><volume>4</volume><issue>7</issue><spage>101085</spage><epage>101085</epage><pages>101085-101085</pages><artnum>101085</artnum><issn>2666-3791</issn><eissn>2666-3791</eissn><abstract>Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Investigating shared genetic components between metabolites and AMD can enhance our understanding of its pathogenesis. We conduct metabolite genome-wide association studies (mGWASs) using multi-ethnic genetic and metabolomic data from up to 28,000 participants. With bidirectional Mendelian randomization analysis involving 16,144 advanced AMD cases and 17,832 controls, we identify 108 putatively causal relationships between plasma metabolites and advanced AMD. These metabolites are enriched in glycerophospholipid metabolism, lysophospholipid, triradylcglycerol, and long chain polyunsaturated fatty acid pathways. Bayesian genetic colocalization analysis and a customized metabolome-wide association approach prioritize putative causal AMD-associated metabolites. We find limited evidence linking urine metabolites to AMD risk. Our study emphasizes the contribution of plasma metabolites, particularly lipid-related pathways and genes, to AMD risk and uncovers numerous putative causal associations between metabolites and AMD risk.
[Display omitted]
•Large-scale metabolite genome-wide association studies identify mQTLs in plasma and urine•Two-sample Mendelian randomization analysis uncovers 108 plasma metabolites associated with AMD•AMD-associated metabolites are enriched in lipid-related pathways•Systematic exploration of metabolite connections with AMD subtypes and lipid biomarkers
In this study, Han et al. conduct large-scale integrative genetic and metabolomic analysis and discover 108 plasma metabolites associated with advanced age-related macular degeneration. The identified metabolites are enriched in pathways of glycerophospholipid metabolism, lysophospholipid, triradylcglycerols, and long-chain polyunsaturated fatty acids, providing insight into their potential in AMD pathogenesis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37348500</pmid><doi>10.1016/j.xcrm.2023.101085</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-3823-7308</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2666-3791 |
| ispartof | Cell reports. Medicine, 2023-07, Vol.4 (7), p.101085-101085, Article 101085 |
| issn | 2666-3791 2666-3791 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10394104 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | age-related macular degeneration Aged AMD Bayes Theorem Canadian Longitudinal Study of Aging CLSA genome-wide association studies Genome-Wide Association Study genomics GWASs HCHS/SOL Health Professionals Follow Up Study Hispanic Community Health Study/Study of Latinos HPFS Humans Macular Degeneration - genetics Macular Degeneration - metabolism Mendelian randomization Metabolome - genetics Metabolomics NHS Nurses’ Health Study UK Biobank |
| title | Integrating genetics and metabolomics from multi-ethnic and multi-fluid data reveals putative mechanisms for age-related macular degeneration |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T03%3A37%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Integrating%20genetics%20and%20metabolomics%20from%20multi-ethnic%20and%20multi-fluid%20data%20reveals%20putative%20mechanisms%20for%20age-related%20macular%20degeneration&rft.jtitle=Cell%20reports.%20Medicine&rft.au=Han,%20Xikun&rft.date=2023-07-18&rft.volume=4&rft.issue=7&rft.spage=101085&rft.epage=101085&rft.pages=101085-101085&rft.artnum=101085&rft.issn=2666-3791&rft.eissn=2666-3791&rft_id=info:doi/10.1016/j.xcrm.2023.101085&rft_dat=%3Cproquest_pubme%3E2829426039%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2829426039&rft_id=info:pmid/37348500&rft_els_id=S2666379123002045&rfr_iscdi=true |