{"doi":"10.1007/s11306-015-0829-0","title":"Gender-specific pathway differences in the human serum metabolome","abstract":"The susceptibility for various diseases as well as the response to treatments differ considerably between men and women. As a basis for a gender-specific personalized healthcare, an extensive characterization of the molecular differences between the two genders is required. In the present study, we conducted a large-scale metabolomics analysis of 507 metabolic markers measured in serum of 1756 participants from the German KORA F4 study (903 females and 853 males). One-third of the metabolites show significant differences between males and females. A pathway analysis revealed strong differences in steroid metabolism, fatty acids and further lipids, a large fraction of amino acids, oxidative phosphorylation, purine metabolism and gamma-glutamyl dipeptides. We then extended this analysis by a network-based clustering approach. Metabolite interactions were estimated using Gaussian graphical models to get an unbiased, fully data-driven metabolic network representation. This approach is not limited to possibly arbitrary pathway boundaries and can even include poorly or uncharacterized metabolites. The network analysis revealed several strongly gender-regulated submodules across different pathways. Finally, a gender-stratified genome-wide association study was performed to determine whether the observed gender differences are caused by dimorphisms in the effects of genetic polymorphisms on the metabolome. With only a single genome-wide significant hit, our results suggest that this scenario is not the case. In summary, we report an extensive characterization and interpretation of gender-specific differences of the human serum metabolome, providing a broad basis for future analyses.","journal":"Metabolomics","year":2015,"id":253,"datarank":0.8565640526062306,"base_score":5.71042701737487,"endowment":5.71042701737487,"self_citation_contribution":0.8565640526062306,"citation_network_contribution":0.0,"self_endowment_contribution":0.8565640526062306,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":301,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.2273,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2015-08-04","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":2338,"name":"Kirstin Mittelstrass","orcid":null,"position":1,"is_corresponding":false},{"id":2339,"name":"Kieu Trinh Do","orcid":null,"position":2,"is_corresponding":false},{"id":2340,"name":"Ferdinand Stückler","orcid":null,"position":3,"is_corresponding":false},{"id":21712,"name":"Cameron D. Palmer","orcid":"0000-0003-3130-1968","position":4,"is_corresponding":false},{"id":2342,"name":"Jerzy Adamski","orcid":"0000-0001-9259-0199","position":5,"is_corresponding":false},{"id":2343,"name":"Annette Peters","orcid":"0000-0001-6645-0985","position":6,"is_corresponding":false},{"id":2344,"name":"Thomas Illig","orcid":"0000-0003-4284-5389","position":7,"is_corresponding":false},{"id":2345,"name":"Florian Kronenberg","orcid":"0000-0003-2229-1120","position":8,"is_corresponding":false},{"id":2346,"name":"Nele Friedrich","orcid":"0000-0002-1017-7622","position":9,"is_corresponding":false},{"id":2347,"name":"Matthias Nauck","orcid":"0000-0002-6678-7964","position":10,"is_corresponding":false},{"id":2348,"name":"Maik Pietzner","orcid":"0000-0003-3437-9963","position":11,"is_corresponding":false},{"id":2349,"name":"Dennis O. Mook-Kanamori","orcid":null,"position":12,"is_corresponding":false},{"id":2350,"name":"Karsten Suhre","orcid":"0000-0001-9638-3912","position":13,"is_corresponding":false},{"id":2351,"name":"Christian Gieger","orcid":"0000-0001-6986-9554","position":14,"is_corresponding":false},{"id":2352,"name":"Harald Grallert","orcid":"0000-0002-6876-9655","position":15,"is_corresponding":false},{"id":42,"name":"Fabian Joachim Theis","orcid":"0000-0002-2419-1943","position":16,"is_corresponding":false},{"id":2353,"name":"Gabi Kastenmüller","orcid":"0000-0002-2368-7322","position":17,"is_corresponding":false},{"id":2354,"name":"Kirstin Mittelstraß","orcid":null,"position":18,"is_corresponding":false},{"id":2355,"name":"Kieu Trinh","orcid":null,"position":19,"is_corresponding":false},{"id":2356,"name":"Janina S. Ried","orcid":null,"position":20,"is_corresponding":false},{"id":2357,"name":"Dennis O. Mook‐Kanamori","orcid":"0000-0002-0182-5122","position":21,"is_corresponding":false},{"id":2337,"name":"Jan Krumsiek","orcid":"0000-0003-4734-3791","position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}