Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/107155 https://doi.org/10.3390/metabo9070127 |
Resumo: | The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 × 10-2-1.8 × 10-5), and 67 across disease stages (FDR q-value: 4.5 × 10-2-1.7 × 10-4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value ≤ 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition. |
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Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohortsage-related macular degenerationmass spectrometrymetabolomicsThe pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 × 10-2-1.8 × 10-5), and 67 across disease stages (FDR q-value: 4.5 × 10-2-1.7 × 10-4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value ≤ 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition.MDPI2019-07-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107155http://hdl.handle.net/10316/107155https://doi.org/10.3390/metabo9070127eng2218-1989Laíns, InêsChung, WonilKelly, Rachel S.Gil, JoãoMarques, MarcoBarreto, PatríciaMurta, Joaquim N.Kim, Ivana K.Vavvas, Demetrios G.Miller, John B.Silva, RufinoLasky-Su, JessicaLiang, LimingMiller, Joan W.Husain, Deebainfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-06-12T09:52:07Zoai:estudogeral.uc.pt:10316/107155Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:31.047135Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts |
title |
Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts |
spellingShingle |
Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts Laíns, Inês age-related macular degeneration mass spectrometry metabolomics |
title_short |
Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts |
title_full |
Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts |
title_fullStr |
Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts |
title_full_unstemmed |
Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts |
title_sort |
Human Plasma Metabolomics in Age-Related Macular Degeneration: Meta-Analysis of Two Cohorts |
author |
Laíns, Inês |
author_facet |
Laíns, Inês Chung, Wonil Kelly, Rachel S. Gil, João Marques, Marco Barreto, Patrícia Murta, Joaquim N. Kim, Ivana K. Vavvas, Demetrios G. Miller, John B. Silva, Rufino Lasky-Su, Jessica Liang, Liming Miller, Joan W. Husain, Deeba |
author_role |
author |
author2 |
Chung, Wonil Kelly, Rachel S. Gil, João Marques, Marco Barreto, Patrícia Murta, Joaquim N. Kim, Ivana K. Vavvas, Demetrios G. Miller, John B. Silva, Rufino Lasky-Su, Jessica Liang, Liming Miller, Joan W. Husain, Deeba |
author2_role |
author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Laíns, Inês Chung, Wonil Kelly, Rachel S. Gil, João Marques, Marco Barreto, Patrícia Murta, Joaquim N. Kim, Ivana K. Vavvas, Demetrios G. Miller, John B. Silva, Rufino Lasky-Su, Jessica Liang, Liming Miller, Joan W. Husain, Deeba |
dc.subject.por.fl_str_mv |
age-related macular degeneration mass spectrometry metabolomics |
topic |
age-related macular degeneration mass spectrometry metabolomics |
description |
The pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness worldwide, remains only partially understood. This has led to the current lack of accessible and reliable biofluid biomarkers for diagnosis and prognosis, and absence of treatments for dry AMD. This study aimed to assess the plasma metabolomic profiles of AMD and its severity stages with the ultimate goal of contributing to addressing these needs. We recruited two cohorts: Boston, United States (n = 196) and Coimbra, Portugal (n = 295). Fasting blood samples were analyzed using ultra-high performance liquid chromatography mass spectrometry. For each cohort, we compared plasma metabolites of AMD patients versus controls (logistic regression), and across disease stages (permutation-based cumulative logistic regression considering both eyes). Meta-analyses were then used to combine results from the two cohorts. Our results revealed that 28 metabolites differed significantly between AMD patients versus controls (false discovery rate (FDR) q-value: 4.1 × 10-2-1.8 × 10-5), and 67 across disease stages (FDR q-value: 4.5 × 10-2-1.7 × 10-4). Pathway analysis showed significant enrichment of glycerophospholipid, purine, taurine and hypotaurine, and nitrogen metabolism (p-value ≤ 0.04). In conclusion, our findings support that AMD patients present distinct plasma metabolomic profiles, which vary with disease severity. This work contributes to the understanding of AMD pathophysiology, and can be the basis of future biomarkers and precision medicine for this blinding condition. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-07-02 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107155 http://hdl.handle.net/10316/107155 https://doi.org/10.3390/metabo9070127 |
url |
http://hdl.handle.net/10316/107155 https://doi.org/10.3390/metabo9070127 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2218-1989 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799134122180870144 |