N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis
<p dir="ltr">N-lactoyl-amino acids (Lac-AA) are emerging as important metabolites with diverse physiological roles. This study integrates metabolomics and genomics to investigate the genetic determinants and clinical relevance of three Lac-AA: N-Lactoyl phenylalanine (Lac-Phe), N-Lac...
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2025
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| _version_ | 1864513524452032512 |
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| author | Asma A Elashi (18464133) |
| author2 | Aleem Razzaq (14779189) Najeha Anwardeen (11924495) Khaled Naja (17886740) Mashael Alshafai (14778607) Ilhame Diboun (3522413) Omar Albagha (8977856) Mohamed A Elrayess (11843435) |
| author2_role | author author author author author author author |
| author_facet | Asma A Elashi (18464133) Aleem Razzaq (14779189) Najeha Anwardeen (11924495) Khaled Naja (17886740) Mashael Alshafai (14778607) Ilhame Diboun (3522413) Omar Albagha (8977856) Mohamed A Elrayess (11843435) |
| author_role | author |
| dc.creator.none.fl_str_mv | Asma A Elashi (18464133) Aleem Razzaq (14779189) Najeha Anwardeen (11924495) Khaled Naja (17886740) Mashael Alshafai (14778607) Ilhame Diboun (3522413) Omar Albagha (8977856) Mohamed A Elrayess (11843435) |
| dc.date.none.fl_str_mv | 2025-09-28T09:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1093/hmg/ddaf152 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/N-Lactoyl_amino_acids_insights_from_metabolite_genome-wide_association_studies_and_phenome-wide_association_analysis/31168186 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Immunology Medical biochemistry and metabolomics N-Lactoyl amino acids mGWAS PheWAS Metabolomics |
| dc.title.none.fl_str_mv | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">N-lactoyl-amino acids (Lac-AA) are emerging as important metabolites with diverse physiological roles. This study integrates metabolomics and genomics to investigate the genetic determinants and clinical relevance of three Lac-AA: N-Lactoyl phenylalanine (Lac-Phe), N-Lactoyl tyrosine (Lac-Tyr), and N-Lactoyl valine (Lac-Tyr). We conducted a metabolome-wide association study (mGWAS) on 2811 participants followed by a phenome-wide association study (PheWAS) and pathway enrichment analysis. Our mGWAS revealed modest genetic contributions to Lac-AA levels, with genome-wide significant loci identified for Lac-Tyr and Lac-Val, but not for Lac-Phe. PheWAS analysis linked these genetic variants to key clinical traits, including white blood cell count, platelet count, and glucose levels. Pathway enrichment highlighted the involvement of Lac-AA in immune-metabolic crosstalk, particularly in inflammation and energy metabolism. These findings suggest that Lac-AA levels are primarily influenced by dynamic metabolic or inflammatory states rather than fixed genetic factors. Our results underscore the potential of Lac-AA as metabolic sensors and biomarkers at the intersection of cellular energy states and systemic inflammation, opening new avenues for research in metabolic and inflammatory disorders.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Human Molecular Genetics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1093/hmg/ddaf152" target="_blank">https://dx.doi.org/10.1093/hmg/ddaf152</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d08ee2329171286d75a6382a89ee6b88 |
| identifier_str_mv | 10.1093/hmg/ddaf152 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/31168186 |
| publishDate | 2025 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysisAsma A Elashi (18464133)Aleem Razzaq (14779189)Najeha Anwardeen (11924495)Khaled Naja (17886740)Mashael Alshafai (14778607)Ilhame Diboun (3522413)Omar Albagha (8977856)Mohamed A Elrayess (11843435)Biological sciencesGeneticsBiomedical and clinical sciencesImmunologyMedical biochemistry and metabolomicsN-Lactoyl amino acidsmGWASPheWASMetabolomics<p dir="ltr">N-lactoyl-amino acids (Lac-AA) are emerging as important metabolites with diverse physiological roles. This study integrates metabolomics and genomics to investigate the genetic determinants and clinical relevance of three Lac-AA: N-Lactoyl phenylalanine (Lac-Phe), N-Lactoyl tyrosine (Lac-Tyr), and N-Lactoyl valine (Lac-Tyr). We conducted a metabolome-wide association study (mGWAS) on 2811 participants followed by a phenome-wide association study (PheWAS) and pathway enrichment analysis. Our mGWAS revealed modest genetic contributions to Lac-AA levels, with genome-wide significant loci identified for Lac-Tyr and Lac-Val, but not for Lac-Phe. PheWAS analysis linked these genetic variants to key clinical traits, including white blood cell count, platelet count, and glucose levels. Pathway enrichment highlighted the involvement of Lac-AA in immune-metabolic crosstalk, particularly in inflammation and energy metabolism. These findings suggest that Lac-AA levels are primarily influenced by dynamic metabolic or inflammatory states rather than fixed genetic factors. Our results underscore the potential of Lac-AA as metabolic sensors and biomarkers at the intersection of cellular energy states and systemic inflammation, opening new avenues for research in metabolic and inflammatory disorders.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Human Molecular Genetics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1093/hmg/ddaf152" target="_blank">https://dx.doi.org/10.1093/hmg/ddaf152</a></p>2025-09-28T09:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1093/hmg/ddaf152https://figshare.com/articles/journal_contribution/N-Lactoyl_amino_acids_insights_from_metabolite_genome-wide_association_studies_and_phenome-wide_association_analysis/31168186CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/311681862025-09-28T09:00:00Z |
| spellingShingle | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis Asma A Elashi (18464133) Biological sciences Genetics Biomedical and clinical sciences Immunology Medical biochemistry and metabolomics N-Lactoyl amino acids mGWAS PheWAS Metabolomics |
| status_str | publishedVersion |
| title | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis |
| title_full | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis |
| title_fullStr | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis |
| title_full_unstemmed | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis |
| title_short | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis |
| title_sort | N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis |
| topic | Biological sciences Genetics Biomedical and clinical sciences Immunology Medical biochemistry and metabolomics N-Lactoyl amino acids mGWAS PheWAS Metabolomics |