Genetic factors shaping the plasma lipidome and the relations to cardiometabolic risk in children and adolescents

EBioMedicine, Journal Year: 2025, Volume and Issue: 112, P. 105537 - 105537

Published: Jan. 2, 2025

Language: Английский

---

The impact of lipidome on breast cancer: a Mendelian randomization study

Lipids in Health and Disease, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 15, 2024

Abstract Objective This study aims to investigate the association between specific lipidomes and risk of breast cancer (BC) using Two-Sample Mendelian Randomization (TSMR) approach Bayesian Model Averaging (BMA-MR) method. Method The analyzed data from large-scale GWAS datasets 179 assess relationship BC across different molecular subtypes. TSMR was employed explore causal relationships, while BMA-MR method carried out validate results. assessed heterogeneity horizontal pleiotropy through Cochran's Q, MR-Egger intercept tests, MR-PRESSO. Moreover, a leave-one-out sensitivity analysis performed evaluate impact individual single nucleotide polymorphisms on MR study. Results By examining lipidome traits as exposures outcome, revealed significant effects glycerophospholipids, sphingolipids, glycerolipids risk. Specifically, for estrogen receptor-positive (ER + BC), phosphatidylcholine ( P < 0.05) phosphatidylinositol (OR: 0.916–0.966, within glycerophospholipids play roles, along with importance (diacylglycerol (OR = 0.923, 0.001) triacylglycerol, OR: 0.894–0.960, 0.05)). However, did not observe noteworthy sphingolipids ER BC. In case receptor-negative − only 1.085, 0.008), 0.909, 0.002) exerted an influence, but protective effect sterols 1.034–1.056, also discovered. prominence minimal in ER-BC. Phosphatidylethanolamine 1.091–1.119, important Conclusions findings reveal that triglycerides levels decreased BC, indicating potential role these lipid molecules. elucidates BC's intricate metabolic pathways, highlighting diverse structural variations may have varying

Language: Английский

---

Characterisation of pregnancy-induced alterations in apolipoproteins and their associations with maternal metabolic risk factors and offspring birth outcomes: a preconception and longitudinal cohort study

EBioMedicine, Journal Year: 2025, Volume and Issue: 112, P. 105562 - 105562

Published: Jan. 21, 2025

Language: Английский

---

Lipidomics unravels lipid changes in osteoarthritis articular cartilage

Annals of the Rheumatic Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Osteoarthritis (OA) is linked to disrupted lipid metabolism. We aimed profile the composition of human articular cartilage, investigate OA-associated lipidome changes, and explore biological effects. Lipidomic profiling computational analyses were performed on chondrocytes (hACs) from non-OA (n = 13) OA 14) hips. Lipid changes confirmed in destabilisation medial meniscus (DMM) mouse model. The effect specific lipids was evaluated by vitro supplementation gene silencing. identified 573 species covering 11 classes hACs. hACs showed distinct profiles. Most ceramides dihydroceramides increased, while cholesteryl esters, diacylglycerols, triacylglycerols, sphingomyelins, hexosylceramides, lactosylceramides predominantly decreased chondrocytes. upregulated contained C18:1, C20:4, or C22:4 side chains. Many downregulated C18:2 odd-chain C17:0. cartilage DMM model paralleled hACs, including C17:0 reduction. Further analysis that deficiency enzyme 2-hydroxyacyl-CoA lyase 1 (HACL1), responsible for fatty acid synthesis, leads accumulation 2-hydroxy C18:0, precursor C17:0, which results a shift an anabolic catabolic state. Our study maps hAC highlights profiles associated with OA. Dysregulation certain lipids, especially acids, HACL1, pathological changes. This understanding opens potential avenues therapies at targeting imbalances slow down treat

Language: Английский

---

A statistical framework for multi-trait rare variant analysis in large-scale whole-genome sequencing studies

Nature Computational Science, Journal Year: 2025, Volume and Issue: 5(2), P. 125 - 143

Published: Feb. 7, 2025

Language: Английский

---

Causal effects of gut microbiota, metabolites, immune cells, liposomes, and inflammatory proteins on anorexia nervosa: A mediation joint multi-omics Mendelian randomization analysis

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

---

Exploring lipidome mediated inflammatory pathways in acute pancreatitis using mendelian randomization

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 8, 2025

Acute pancreatitis (AP) is a severe gastrointestinal condition with an increasing incidence of hyperlipidemic etiology. The investigation employed two-sample, bidirectional Mendelian randomization method to investigate potential causal relationship between lipidome profiles, inflammatory mediators, and AP. Exploration genetic variants across the genome in study population 10,630 AP cases 844,679 non-AP individuals revealed multiple entities significantly associated risk. identified 23 lipid species unidirectional effects on after accounting for heterogeneity, pleiotropy, reverse causation. Additionally, five factors (CD5, IL-13, MMP-1, STAMBP, TNFRSF9) showed significant Further analysis elucidated intricate interplay specific mediators influencing incidence. Notably, Sterol ester (27:1/20:4) several phosphatidylcholine species, including PC (17:0_20:4), (18:0_20:4), (18:0_20:5), (O-18:2_20:4), were negatively This protective effect was partially mediated through decreased levels markers, particularly STAMBP MMP-1. found that these phosphatidylcholines sterol esters reduced pro-inflammatory factors, thereby potentially mitigating Conversely, Phosphatidylinositol (16:0_18:1) demonstrated positive association detrimental by increased MMP-1 suggesting mechanism. provides evidence this phosphatidylinositol may exacerbate risk promoting pathways. These findings elucidate complex metabolites, inflammation, pathogenesis, informing novel therapeutic strategies. highlights utility uncovering It underscores requirement further into molecular mechanisms underlying lipid-mediated inflammation AP, roles modulating responses. studies are warranted confirm our observations laboratory models assess their translational value developing preventive

Language: Английский

---

Causal relationships between plasma lipidome and diabetic neuropathy: a Mendelian randomization study

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 15, 2025

Dyslipidemia is closely related to diabetic neuropathy. This study examined the potential causal relationship involving 179 lipid species and disease. The pooled data on neuropathy were obtained from previous genome-wide association studies (GWAS). A Mendelian Randomization (MR) method was employed investigate link, robustness of findings confirmed through comprehensive sensitivity analyses. Genetically, phosphatidylcholine might be associated with risk Upon adjusting for multiple comparisons, higher levels (16:0_20:2) (OR = 0.82, 95%CI: 0.73-0.91; P < 0.001, FDR 0.033) (16:1_18:1) 0.77, 0.67-0.88; 0.019) are a decreased Further multivariable MR (MVMR) analysis demonstrated effect genetically predicted remained after body mass index (BMI) glycated hemoglobin (HbA1c). Sensitivity assessments have these findings, revealing no evidence heterogeneity or pleiotropy. Our research linked certain risk, suggesting that targeting lipids could therapeutic strategy in clinical trials addressing this condition.

Language: Английский

---

Genetically predicted causal link between the plasma lipidome and pancreatic diseases: a bidirectional Mendelian randomization study

Frontiers in Nutrition, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 15, 2025

Recent studies have increasingly emphasized the strong correlation between lipidome and risk of pancreatic diseases. To determine causality, a Mendelian randomization (MR) analysis was performed to identify connections Statistics from genome-wide association study plasma lipidome, which included diverse array 179 lipid species, were obtained GeneRISK cohort with 7,174 participants. Genetic associations four types pancreatitis cancer sourced R11 release FinnGen consortium. Two datasets UK Biobank employed as validation cohort. MR conducted assess relationship genetically predicted these Inverse variance weighted adopted main statistical method. Bayesian for further verification. The MR-Egger intercept test pleiotropy Cochrane's Q statistics heterogeneity ensure robustness. yielded significant evidence that 26, 25, 2, 19 species correlated outcomes pancreatitis, 8 cancer. Notably, sterol ester (27:1/20:2) levels (OR: 0.84, 95% CI: 0.78-0.90, P = 5.79 × 10-7) significantly associated acute phosphatidylcholine (17:0_20:4) 0.89, 0.84-0.94, 1.78 10-4) (27:1/20:4) 0.90, 0.86-0.95, 2.71 chronic after Bonferroni-corrected test. As validation, 14 9 Biobank. Some classes showed effects both in consortium datasets. findings this indicate potential genetic predisposition linking diseases good prospects future disease clinical trials.

Language: Английский

---

Evaluating the association between lipidome and female reproductive diseases through comprehensive Mendelian randomization analyses

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 19, 2025

This study aimed to assess the causal relationship between lipidome and female reproductive diseases (FRDs) using an advanced series of Mendelian randomization (MR) methods. utilized genome-wide association (GWAS) summary statistics encompassing 179 lipidomes six prevalent FRDs, namely polycystic ovary syndrome (PCOS), endometriosis, uterine fibroid, infertility, endometrial cancer, ovarian cancer. The two-sample MR (TSMR) approach was employed investigate relationships, with further validation false discovery rate (FDR) multivariable (MVMR) Subsequently, a range comprehensive evaluations were performed, including sensitivity analysis, mediation reverse steiger test. Examining traits as exposures 6 FRDs outcomes, this identified significant effects 56 lipids on FRDs. Following multiple testing correction MVMR validation, sphingomyelin (d38:2) found have protective effect against PCOS (β = -0.104, 95% CI: -0.199 ~ -0.010, P 0.031). Phosphatidylcholine (18:0_22:6) associated decreased risk developing fibroid -0.111, -0.201~ -0.021, 0.016), sterol ester (27:1/20:3) showed significance in cancer -0.248, -0.443 -0.053, 0.013). Conversely, phosphatidylethanolamine (18:2_0:0) increased endometriosis 0.183, 0.015 0.350, 0.033), while (27:1/18:1) posed influence 1.007, 0.925 1.089, < 0.001), phosphatidylcholine (16:0_22:6) 0.229, 0.039 0.420, 0.018). Furthermore, it determined that associations these profiles independent BMI, obesity, diabetes, smoking, alcohol use, physical activity, inflammation, depression, waist-hip ratio, vitamin D, dehydroepiandrosterone sulphate, sex hormone binding globulin, testosterone levels. Most outcomes passed consistent tests without evidence heterogeneity, pleiotropy, or causality. results indicated close specific lipidomes, particularly sphingomyelin, lysophosphatidylethanolamine, cholesterol ester, phosphatidylcholines, These lipid species may potentially serve biomarkers future drug targets for treatment

Language: Английский

---