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Background: Cardiovascular diseases (CVDs) comprise major causes of death worldwide, leading to extensive burden on populations and societies. Alterations in normal lipid profiles, i.e., dyslipidemia, comprise important risk factors for CVDs. However, there is lack of comprehensive evidence on the genetic contribution to dyslipidemia in highly admixed populations. The identification of single nucleotide polymorphisms (SNPs) linked to blood lipid traits in the Brazilian population was based on genome-wide associations using data from the São Paulo Health Survey with Focus on Nutrition (ISA-Nutrition). Methods: A total of 667 unrelated individuals had genetic information on 330,656 SNPs available, and were genotyped with Axiom™ 2.0 Precision Medicine Research Array. Genetic associations were tested at the 10− 5 significance level for the following phenotypes: low-density lipoprotein cholesterol (LDL-c), very low-density lipoprotein cholesterol (VLDL-c), high-density lipoprotein cholesterol (HDL-c), HDL-c/LDL-c ratio, triglycerides (TGL), total cholesterol, and non-HDL-c. Results: There were 19 significantly different SNPs associated with lipid traits, the majority of which corresponding to intron variants, especially in the genes FAM81A, ZFHX3, PTPRD, and POMC. Three variants (rs1562012, rs16972039, and rs73401081) and two variants (rs8025871 and rs2161683) were associated with two and three phenotypes, respectively. Among the subtypes, non-HDL-c had the highest proportion of associated variants. Conclusions: The results of the present genome-wide association study offer new insights into the genetic structure underlying lipid traits in underrepresented populations with high ancestry admixture. The associations were robust across multiple lipid phenotypes, and some of the phenotypes were associated with two or three variants. In addition, some variants were present in genes that encode ncRNAs, raising important questions regarding their role in lipid metabolism. [ABSTRACT FROM AUTHOR]

Aims: Recent studies have indicated an association between intestinal flora and lipids. However, observational studies cannot indicate causality. In this study, we aimed to investigate the potentially causal relationships between the intestinal flora and blood lipids. Methods: We performed a bidirectional two-sample Mendelian Randomization (MR) analysis to investigate the causal relationship between intestinal flora and blood lipids. Summary statistics of genome-wide association studies (GWASs) for the 211 intestinal flora and blood lipid traits (n = 5) were obtained from public datasets. Five recognized MR methods were applied to assess the causal relationship with lipids, among which, the inverse-variance weighted (IVW) regression was used as the primary MR method. A series of sensitivity analyses were performed to test the robustness of the causal estimates. Results: The results indicated a potential causal association between 19 intestinal flora and dyslipidemia in humans. Genus Ruminococcaceae, Christensenellaceae, Parasutterella, Terrisporobacter, Parabacteroides, Class Erysipelotrichia, Family Erysipelotrichaceae, and order Erysipelotrichales were associated with higher dyslipidemia, whereas genus Oscillospira, Peptococcus, Ruminococcaceae UCG010, Ruminococcaceae UCG011, Dorea, and Family Desulfovibrionaceae were associated with lower dyslipidemia. After using the Bonferroni method for multiple testing correction, Only Desulfovibrionaceae [Estimate = -0.0418, 95% confidence interval [CI]: 0.9362–0.9826, P = 0.0007] exhibited stable and significant negative associations with ApoB levels. The inverse MR analysis did not find a significant causal effect of lipids on the intestinal flora. Additionally, no significant heterogeneity or horizontal pleiotropy for IVs was observed in the analysis. Conclusion: The study suggested a causal relationship between intestinal flora and dyslipidemia. These findings will provide a meaningful reference to discover dyslipidemia for intervention to address the problems in the clinic. [ABSTRACT FROM AUTHOR]

Objectives: In response to the controversy surrounding observational studies of the association between lipid profiles and the risk of insomnia, the aim of this study was to analyze lipid profiles, including triglycerides (TG), apolipoprotein A-1 (ApoA-1), apolipoprotein B (ApoB) and lipoprotein A (LPA), in a European population to further assess the causal relationship between these lipid types and insomnia. Materials and methods: This study explores the causal effect of lipid profiles on insomnia based on a genome-wide association study (GWAS)-derived public dataset using two-sample and multivariate Mendelian randomization (MVMR) analysis. The main MR analyses used inverse variance weighting (IVW) odds ratio (OR), and the sensitivity analyses included weighted median (WM) and MR‒Egger. Results: Both MR and MVMR showed that lowering ApoA-1 and LPA levels had causal effects on the risk of insomnia [MR: per 10 units, ApoA-1: OR: 0.7546, 95% CI: 0.6075–0.9372, P = 0.011; LPA: OR: 0.8392, 95% CI: 0.7202–0.9778, P = 0.025; MVMR: per 10 units, ApoA-1: OR: 0.7600, 95% CI: 0.6362–0.9079, P = 0.002; LPA, OR: 0.903, 95% CI: 0.8283–0.9845, P = 0.021]. There were no causal effects of TG or ApoB on insomnia (all P > 0.05). The MR‒Egger intercept test, funnel plot, and IVW methods all suggested an absence of strong directional pleiotropy, and leave-one-out permutation analysis did not detect any single single-nucleotide polymorphism that had a strong influence on the results. Conclusion: Elevated levels of ApoA-1 and LPA were independently and causally associated with the risk of insomnia, suggesting that elevated ApoA-1 and LPA levels may contribute to a reduced risk of insomnia. [ABSTRACT FROM AUTHOR]

Objective: Several research has considered the potential correlation between periodontitis and serum lipids. However, serum lipid profiles correlation with periodontitis remains largely unknown. The investigation objective was to examine periodontitis correlation with serum lipid levels using a bidirectional Mendelian randomization (MR) analysis. Methods: The study employed a bidirectional MR analysis with two samples, utilizing a freely accessible genome-wide association study (GWAS). Furthermore, the primary analysis employed the inverse variance weighted (IVW) method. To determine whether the lipid profiles were associated with periodontitis, a variety of sensitivity analyses (including MR-Egger regression, MR-PRESSO, and weighted median), as well as multivariable MR, were employed. Results: MR analysis performed by IVW did not reveal any relationship between periodontitis and low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), or total cholesterol (TC). It was also found that LDL, HDL, TG, and TC were not associated to periodontitis. Furthermore, the MR estimations exhibited consistency with other MR sensitivity and multivariate MR (MVMR) analyses. These results show that the correlation between serum lipid levels and periodontitis could not be established. Conclusion: The finding indicates a negligible link between periodontitis and serum lipid levels were identified, despite previous observational studies reporting a link between periodontitis and serum lipid levels. [ABSTRACT FROM AUTHOR]

Background: This study aims to comprehensively investigate the phenotypic and genetic relationships between four common lipids (high-density lipoprotein cholesterol, HDL-C; low-density lipoprotein cholesterol, LDL-C; total cholesterol, TC; and triglycerides, TG), chronic kidney disease (CKD), and estimated glomerular filtration rate (eGFR). Methods: We first investigated the observational association of lipids (exposures) with CKD (primary outcome) and eGFR (secondary outcome) using data from UK Biobank. We then explored the genetic relationship using summary statistics from the largest genome-wide association study of four lipids (N = 1,320,016), CKD (Ncase = 41,395, Ncontrol = 439,303), and eGFR(N = 567,460). Results: There were significant phenotypic associations (HDL-C: hazard ratio (HR) = 0.76, 95%CI = 0.60–0.95; TG: HR = 1.08, 95%CI = 1.02–1.13) and global genetic correlations (HDL-C: r g = − 0.132, P = 1.00 × 10–4; TG: r g = 0.176; P = 2.66 × 10–5) between HDL-C, TG, and CKD risk. Partitioning the whole genome into 2353 LD-independent regions, twelve significant regions were observed for four lipids and CKD. The shared genetic basis was largely explained by 29 pleiotropic loci and 36 shared gene-tissue pairs. Mendelian randomization revealed an independent causal relationship of genetically predicted HDL-C (odds ratio = 0.91, 95%CI = 0.85–0.98), but not for LDL-C, TC, or TG, with the risk of CKD. Regarding eGFR, a similar pattern of correlation and pleiotropy was observed. Conclusions: Our work demonstrates a putative causal role of HDL-C in CKD and a significant biological pleiotropy underlying lipids and CKD in populations of European ancestry. Management of low HDL-C levels could potentially benefit in reducing the long-term risk of CKD. [ABSTRACT FROM AUTHOR]

Background: Low-density lipoprotein (LDL)-cholesterol is positively associated with cardiovascular disease (CVD) and inversely associated with type 2 diabetes, which could detract from lipid modification. Here, we examined whether lipid traits potentially relevant to CVD aetiology, i.e. apolipoprotein B (apoB), triglycerides (TG) and lipoprotein(a) [Lp(a)] exhibited the same associations. We investigated sex-specifically, including the role of sex hormones, because sex disparities exist in lipid profile and type 2 diabetes. We also replicated where possible. Methods: We used Mendelian randomization (MR) to examine sex-specific associations of apoB, TG and Lp(a) with type 2 diabetes, HbA1c, fasting insulin, fasting glucose, testosterone and estradiol in the largest relevant sex-specific genome-wide association studies (GWAS) in people of European ancestry and replicated where possible. We also assessed sex-specific associations of liability to type 2 diabetes with apoB, TG and Lp(a). Results: Genetically predicted apoB and Lp(a) had little association with type 2 diabetes or glycemic traits in women or men. Genetically predicted higher TG was associated with higher type 2 diabetes risk [odds ratio (OR) 1.44 per standard deviation (SD), 95% confidence interval (CI) 1.26 to 1.65], HbA1c and fasting insulin specifically in women. Higher TG was associated with lower testosterone in women and higher testosterone in men, but with lower estradiol in men and women. Genetic liability to type 2 diabetes was associated with higher TG in women, and possibly with lower apoB in men. Conclusions: Lipid traits potentially relevant to CVD aetiology do not exhibit contrasting associations with CVD and type 2 diabetes. However, higher TG is associated with higher type 2 diabetes risk and glycemic traits, which in turn further increases TG specifically in women, possibly driven by sex hormones. [ABSTRACT FROM AUTHOR]