{"doi":"10.1101/2020.01.15.19015206","title":"Sex differences in cardiometabolic traits at four life stages: cohort study with repeated metabolomics","abstract":"Abstract Background Males experience higher rates of coronary heart disease (CHD) than females, but the circulating traits underpinning this difference are poorly understood. We examined sex differences in detailed cardiometabolic traits measured at four life stages, spanning childhood to middle adulthood. Methods and Results Data were from the Avon Longitudinal Study of Parents and Children cohort study. 229 traits quantified from targeted metabolomics (nuclear magnetic resonance spectroscopy) including lipoprotein subclass-specific cholesterol and triglycerides, amino acids, glucose, and inflammatory glycoprotein acetyls were measured repeatedly in offspring (Generation 1 (G1)) born in 1991-92 and once in their parents (Generation 0 (G0)). Measurements in G1 were once in childhood (mean age 8y), twice in adolescence (16y and 18y) and once in early adulthood (25y), and in G0 once in middle adulthood (50y). Linear regression models were used to examine differences in standardized traits for males compared with females on each occasion (serial cross-sectional associations). 7,727 G1s (49% male) and 6,500 G0s (29% male) contributed to analyses. At age 8y, total lipids in very-low-density lipoproteins (VLDL) were lower in males than females; levels were higher in males than females at age 16y and were higher still by age 18y and age 50y (in G0) for medium-or-larger subclasses. Larger sex differences at older ages were most pronounced for triglycerides in VLDL – e.g. male levels were 0.19 standard deviation (SD) units (95% CI=0.12, 0.26) higher at age 18y, 0.50 SD (95% CI=0.42, 0.57) higher at age 25y, and 0.62 SD (95% CI=0.55, 0.68) higher at age 50y. Cholesterol in VLDL and low-density lipoproteins (LDL) was generally lower in males, with inconsistent sex differences across ages. Apolipoprotein-B was generally lower in males than females. Branched chain amino acids were consistently higher in males after age 8y with the largest sex difference of all traits at all ages seen for leucine at age 50y (1.53 SD, 95% CI=1.47, 1.58 higher in males compared with females). Males had consistently lower glycoprotein acetyls across ages. Conclusions Our results suggest that males begin to have higher VLDL triglycerides in adolescence, and that this sex difference is larger at older ages. Sex differences in other CHD-related traits, including LDL cholesterol, apolipoprotein-B, and inflammatory glycoproteins, show the opposite pattern with age, with higher levels among females. Higher triglyceride content may therefore be a key factor underpinning the higher age-adjusted rate of CHD among males; causal analyses of this and other traits are needed to understand whether they differentially affect CHD risk among males and females.","journal":"medRxiv","year":2020,"id":121931,"datarank":0.39777748044238187,"base_score":1.791759469228055,"endowment":1.791759469228055,"self_citation_contribution":0.26876392038420827,"citation_network_contribution":0.1290135600581736,"self_endowment_contribution":0.26876392038420827,"citer_contribution":0.1290135600581736,"corpus_percentile":54.0573992418968,"corpus_rank":5940,"citation_count":5,"citer_count":2,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.7403,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":536599,"name":"Diana L. Santos Ferreira","orcid":"0000-0001-8923-0117","position":1,"is_corresponding":false},{"id":271813,"name":"Abigail Fraser","orcid":"0000-0002-7741-9470","position":2,"is_corresponding":false},{"id":270842,"name":"Ana Gonçalves Soares","orcid":"0000-0003-2763-4647","position":3,"is_corresponding":false},{"id":45191,"name":"Laura D Howe","orcid":"0000-0003-3357-2796","position":4,"is_corresponding":false},{"id":477929,"name":"Deborah A. Lawlor","orcid":null,"position":5,"is_corresponding":false},{"id":562147,"name":"David Carslake","orcid":"0000-0003-2916-4546","position":6,"is_corresponding":false},{"id":1528,"name":"George Davey Smith","orcid":"0000-0002-1407-8314","position":7,"is_corresponding":false},{"id":481682,"name":"Linda M. O’Keeffe","orcid":"0000-0002-0003-0774","position":8,"is_corresponding":false},{"id":251130,"name":"Joshua A. Bell","orcid":"0000-0001-6892-8786","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:14:46.979435Z","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":[]}