Genetic Perspective Research Articles

The causal effect of Alzheimer's disease and family history of Alzheimer's disease on non-ischemic cardiomyopathy and left ventricular structure and function: a Mendelian randomization study.

Previous studies have shown that Alzheimer's disease (AD) can cause myocardial damage. However, whether there is a causal association between AD and non-ischemic cardiomyopathy (NICM) remains unclear. Using a comprehensive two-sample Mendelian randomization (MR) method, we aimed to determine whether AD and family history of AD (FHAD) affect left ventricular (LV) structure and function and lead to NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). The summary statistics for exposures [AD, paternal history of AD (PH-AD), and maternal history of AD (MH-AD)] and outcomes (NICM, HCM, DCM, and LV traits) were obtained from the large European genome-wide association studies. The causal effects were estimated using inverse variance weighted, MR-Egger, and weighted median methods. Sensitivity analyses were conducted, including Cochran's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier, MR Steiger test, leave-one-out analysis, and the funnel plot. Genetically predicted AD was associated with a lower risk of NICM [odds ratio (OR) 0.9306, 95% confidence interval (CI) 0.8825-0.9813, p = 0.0078], DCM (OR 0.8666, 95% CI 0.7752-0.9689, p = 0.0119), and LV remodeling index (OR 0.9969, 95% CI 0.9940-0.9998, p = 0.0337). Moreover, genetically predicted PH-AD was associated with a decreased risk of NICM (OR 0.8924, 95% CI 0.8332-0.9557, p = 0.0011). MH-AD was also strongly associated with a decreased risk of NICM (OR 0.8958, 95% CI 0.8449-0.9498, p = 0.0002). Different methods of sensitivity analysis demonstrated the robustness of the results. Our study revealed that AD and FHAD were associated with a decreased risk of NICM, providing a new genetic perspective on the pathogenesis of NICM.

Beyond the Tailbone: A Family's Journey Through Caudal Regression Syndrome—A Triple Sibship

BackgroundCaudal regression syndrome (CRS), also known as caudal agenesis, results from abnormal development of the caudal aspect of the spinal cord and vertebral column due to an earlier abnormality of gastrulation. ResultsThis report showcases a unique scenario where three siblings, devoid of any prior family history or identifiable risk factors, exhibit symptoms of CRS and receive care at a government-run tertiary facility dedicated to children's health. In establishing a concrete diagnosis, we relied on skeletal surveys, comprehensive symptom evaluation, and medical history assessment. Additionally, we recommended further investigation through magnetic resonance imaging and genetic testing to attain a more in-depth understanding and confirmation of the condition. Unfortunately, the financial constraints faced by the parents led to the unfeasibility of pursuing these advanced diagnostic options. Given the rarity of this syndrome and the limited existing literature, our report is a significant contribution. It marks the first comprehensive exploration of CRS from the genetic and familial predisposition perspective, shedding new light on this rare condition. ConclusionThis case series pioneers our understanding of the familial and genetic connections between CRS and sacral agenesis. Strikingly, each subsequent generation has experienced more severe manifestations earlier, furnishing compelling evidence that underpins the genetic predisposition to CRS.

Genetic parameters, GWAS and selection perspective on gestation length in 16 French cattle breeds.

In this paper, we present a comprehensive study of gestation length (GL) in 16 cattle breeds by using large genotype and animal record databases. Data included over 20 million gestations since 2000 and genotypes from one million calves. The study addressed the GL variability within and between breeds, estimation of its direct and maternal heritability coefficients, association with fitness and several economic traits, and QTL detection. The breed average GL varied from 279.7 to 294.4 d, in Holstein and Blonde d'Aquitaine breeds, respectively. Standard deviations per breed were similar and ranged from 5.2 to 5.8 d. Direct heritability (i.e., for GL defined as a trait of the calf) was moderate to high (h2 = 0.40 to 0.67), whereas the maternal heritability was low (0.04 to 0.06). Extreme breeding values for GL were strongly associated with a higher mortality during the first 2 d of life and were associated with milk production of dams for dairy breeds and precocity of females. Finally, several QTL were detected affecting GL with cumulated effects up to a few days, and at least 2 QTL were found to be shared between different breeds. Our study highlights the risks that would be associated with selection toward a reduced gestation length. Further genomic studies are needed to identify the causal variants, and their association with juvenile mortality and other economic traits.

Genetic and phenotypic associations of frailty with cardiovascular indicators and behavioral characteristics

IntroductionFrailty Index (FI) is a common measure of frailty, which has been advocated as a routine clinical test by many guidelines. The genetic and phenotypic relationships of FI with cardiovascular indicators (CIs) and behavioral characteristics (BCs) are unclear, which has hampered ability to monitor FI using easily collected data. ObjectivesThis study is designed to investigate the genetic and phenotypic associations of frailty with CIs and BCs, and further to construct a model to predict FI. MethodGenetic relationships of FI with 288 CIs and 90 BCs were assessed by the cross-trait LD score regression (LDSC) and Mendelian randomization (MR). The phenotypic data of these CIs and BCs were integrated with a machine-learning model to predict FI of individuals in UK-biobank. The relationships of the predicted FI with risks of type 2 diabetes (T2D) and neurodegenerative diseases were tested by the Kaplan-Meier estimator and Cox proportional hazards model. ResultsMR revealed putative causal effects of seven CIs and eight BCs on FI. These CIs and BCs were integrated to establish a model for predicting FI. The predicted FI is significantly correlated with the observed FI (Pearson correlation coefficient = 0.660, P-value = 4.96 × 10-62). The prediction model indicated “usual walking pace” contributes the most to prediction. Patients who were predicted with high FI are in significantly higher risk of T2D (HR = 2.635, P < 2 × 10-16) and neurodegenerative diseases (HR = 2.307, P = 1.62 × 10-3) than other patients. ConclusionThis study supports associations of FI with CIs and BCs from genetic and phenotypic perspectives. The model that is developed by integrating easily collected CIs and BCs data in predicting FI has the potential to monitor disease risk.

Transfer of embryos with positive PGT-M results: Genetic Counselors' perspectives and ethical considerations.

Increasing numbers of fertility patients use preimplantation genetic testing for monogenic conditions (PGT-M) during invitro fertilization (IVF). While PGT-M is primarily used to avoid implanting embryos with a monogenic condition, patients can request to transfer an embryo with the monogenic condition (positive embryo transfer), especially in cases where an IVF cycle results in no unaffected embryos. Transferring embryos with known disease-causing variants raises ethical concerns. There is limited understanding about how stakeholders in the assisted reproductive technology (ART) field approach these issues. In this study, genetic counselors were sent a survey to gather insight into their views about transferring embryos with different monogenic conditions. N = 99 genetic counselors completed the survey, 22 of whom had experience with patients requesting or deciding to transfer an embryo with a monogenic condition (positive embryo transfer experience). Most participants, including those with positive embryo transfer experience, were supportive of positive embryo transfer, regardless of the genetic condition. While participating genetic counselors were largely supportive of all patient decisions, they reported increased moral uneasiness around transferring embryos with life-limiting monogenic conditions, such as Huntington's disease. Further investigation into the experiences of genetic counselors who have experienced positive embryo transfer requests in practice can help delineate the ethical questions that ART providers face in this context and clarify how genetic counselors can contribute to establishing guidelines in the ART field.

Unraveling the Link: Mendelian Randomization Reveals Causal Relationship Between Selenium and Metabolic Syndrome.

Observational studies have linked selenium and metabolic syndrome (MetS), but the causality remains unclear. Therefore, this study intends to determine the causal relationship between selenium and the risk of MetS and its component features [body mass index (BMI), waist circumference adjusted for BMI (WCadjBMI), triglycerides (TC), HDL-cholesterol (HDL-C), fasting blood glucose (FBG), fasting blood insulin (FBI), systolic blood pressure (SBP), and diastolic blood pressure (DBP)]. This study was designed as the two-sample Mendelian randomization (MR), and genetic variants were obtained from the genome-wide association studies. The inverse variance weighted (IVW) was applied as the primary method, and the MR-Egger, weighted median, and MR-PRESSO were supplemented to assess its robustness. The Bonferroni method was used to correct p-values for multiple tests. Genetically incremented selenium level was related to higher odds ratios of developing the MetS (OR = 1.054, 95% CI = 1.016-1.094, p = 0.0049). As for components, significant causal links were identified between selenium and BMI (β = 0.015, p = 1.321 × 10-5), WCadjBMI (β = 0.033, p = 2.352 × 10-4), HDL-C (β = -0.036, p = 1.352 × 10-8), FBG (β = 0.028, p = 0.001), and FBI (β = 0.028, p = 0.002). No significant association was discovered for SBP (β = -0.076, p = 0.218) and DBP (β = 0.054, p = 0.227). These results were generally supported by the weighted median and MR-PRESSO methods. Our study provided evidence of the causal effect of selenium on MetS risk from the genetic perspective in the European population, and further investigation across diverse populations was warranted.

A Review of Type 1 and Type 2 Intraductal Papillary Neoplasms of the Bile Duct.

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs.

Unveiling Promising Neuroimaging Biomarkers for Schizophrenia Through Clinical and Genetic Perspectives.

Schizophrenia is a complex and serious brain disorder. Neuroscientists have become increasingly interested in using magnetic resonance-based brain imaging-derived phenotypes (IDPs) to investigate the etiology of psychiatric disorders. IDPs capture valuable clinical advantages and hold biological significance in identifying brain abnormalities. In this review, we aim to discuss current and prospective approaches to identify potential biomarkers for schizophrenia using clinical multimodal neuroimaging and imaging genetics. We first described IDPs through their phenotypic classification and neuroimaging genomics. Secondly, we discussed the applications of multimodal neuroimaging by clinical evidence in observational studies and randomized controlled trials. Thirdly, considering the genetic evidence of IDPs, we discussed how can utilize neuroimaging data as an intermediate phenotype to make association inferences by polygenic risk scores and Mendelian randomization. Finally, we discussed machine learning as an optimum approach for validating biomarkers. Together, future research efforts focused on neuroimaging biomarkers aim to enhance our understanding of schizophrenia.

A comprehensive genome-wide cross-trait analysis of sexual factors and uterine leiomyoma.

Age at first sexual intercourse (AFS) and lifetime number of sexual partners (NSP) may influence the pathogenesis of uterine leiomyoma (UL) through their associations with hormonal concentrations and uterine infections. Leveraging summary statistics from large-scale genome-wide association studies conducted in European ancestry for each trait (NAFS = 214,547; NNSP = 370,711; NUL = 302,979), we observed a significant negative genomic correlation for UL with AFS (rg = -0.11, P = 7.83×10-4), but not with NSP (rg = 0.01, P = 0.62). Four specific genomic regions were identified as contributing significant local genetic correlations to AFS and UL, including one genomic region further identified for NSP and UL. Partitioning SNP-heritability with cell-type-specific annotations, a close clustering of UL with both AFS and NSP was identified in immune and blood-related components. Cross-trait meta-analysis revealed 15 loci shared between AFS/NSP and UL, including 7 novel SNPs. Univariable two-sample Mendelian randomization (MR) analysis suggested no evidence for a causal association between genetically predicted AFS/NSP and risk of UL, nor vice versa. Multivariable MR adjusting for age at menarche or/and age at natural menopause revealed a significant causal effect of genetically predicted higher AFS on a lower risk of UL. Such effect attenuated to null when age at first birth was further included. Utilizing participant-level data from the UK Biobank, one-sample MR based on genetic risk scores yielded consistent null findings among both pre-menopausal and post-menopausal females. From a genetic perspective, our study demonstrates an intrinsic link underlying sexual factors (AFS and NSP) and UL, highlighting shared biological mechanisms rather than direct causal effects. Future studies are needed to elucidate the specific mechanisms involved in the shared genetic influences and their potential impact on UL development.

Smoking may increase the usage of antidepressant: evidence from genomic perspective analysis.

This study uses the two-sample Mendelian randomization (TSMR) method to explore the causal relationships between smoking initiation (SMKI), never smoking (NSMK), past tobacco smoking (PTSMK), and the usage of antidepressants (ATD). Single-nucleotide polymorphisms (SNPs) with genome-wide significance (P < 5E-08) related to SMKI, NSMK, and PTSMK were selected from the genome-wide association study (GWAS) database as instrumental variables (IVs). The main method, inverse variance weighted (IVW), was utilized to investigate the causal relationship. The results demonstrated a positive causal relationship between SMKI and ATD use, where SMKI leads to an increase in ATD use. Conversely, NSMK and PTSMK showed a negative causal relationship with ATD use, meaning that NSMK and PTSMK lead to a reduction in ATD use. Additionally, sensitivity analysis showed that the results of this study were robust and reliable. Using the TSMR method and from a genetic perspective, this study found that SMKI leads to an increase in ATD use, while NSMK and PTSMK reduce ATD use.

Exploring the potential causal effects of food preferences on irritable bowel syndrome risk: A two-sample Mendelian randomization study.

Irritable bowel syndrome (IBS) is a common disorder in gut-brain interaction. Diet plays an important role in the pathophysiology of IBS. Therefore, we aimed to explore the potential causal effects of food-liking on IBS to provide better diet advice for patients. Single-nucleotide polymorphisms associated with food-liking were selected as instrumental variables, which were obtained from the latest genome-wide association study (GWAS) conducted on 161 625 participants. The summary data of genetic associations with IBS were obtained from a recent GWAS with 433 201 European controls and 53 400 cases. We used inverse variance weighting as the main analysis. Sensitivity analyses were conducted to detect horizontal pleiotropy and heterogeneity. Significant evidence revealed the protective effects of a vegetarian diet-liking on IBS, including asparagus, avocadoes, globe artichoke, aubergine, and black olives, while onion-liking showed potential deleterious effects. For meat and fish, preference for sardines and fried fish was marginally associated with IBS risk, but salami and salmon were potential protective factors. In terms of desserts and dairy products, preferences for cake icing, ketchup, and cheesecake were suggestively associated with higher IBS risk, while goat cheese-liking was marginally correlated with lower IBS risk. Additionally and suggestively, significant causal effects of IBS on increased preferences for globe artichoke and salami were also found in a reverse Mendelian randomization (MR) study. Our study revealed potential causal associations between food preference and IBS from a genetic perspective, which provides a dietary reference for such patients.

The genetic control of herkogamy.

Herkogamy is the spatial separation of anthers and stigmas within complete flowers, and is a key floral trait that promotes outcrossing in many angiosperms. The degree of separation between pollen-producing anthers and receptive stigmas has been shown to influence rates of self-pollination amongst plants, with a reduction in herkogamy increasing rates of successful selfing in self-compatible species. Self-pollination is becoming a critical issue in horticultural crops grown in environments where biotic pollinators are limited, absent, or difficult to utilise. In these cases, poor pollination results in reduced yield and misshapen fruit. Whilst there is a growing body of work elucidating the genetic basis of floral organ development, the genetic and environmental control points regulating herkogamy are poorly understood. A better understanding of the developmental and regulatory pathways involved in establishing varying degrees of herkogamy is needed to provide insights into the production of flowers more adept at selfing to produce consistent, high-quality fruit. This review presents our current understanding of herkogamy from a genetics and hormonal perspective.

Sarcopenia as a Risk Factor for Alzheimer's Disease: Genetic and Epigenetic Perspectives.

Sarcopenia, defined as the age-associated loss of muscle mass and increased fragility with age, is increasing worldwide. The condition often precedes the development of Alzheimer's disease, thereby decreasing the levels of mobility and physical activity in those affected. Indeed, the loss of muscle mass has, in some studies, been associated with an increased risk of Alzheimer's disease and other dementias. However, a detailed understanding of the interplay between both conditions is not available and needs to be thoroughly addressed. In the following review, we focus on several genes, specifically APOE, BDNF, ACE, FTO, and FNDC5, that have been associated with both conditions. We also discuss the epigenetic regulation of each of these genes along with non-coding RNAs (ncRNAs) that may have a role in the development of both the sarcopenic and Alzheimer's disease phenotypes. Finally, we assert that the application of systems biology will unravel the relationship between sarcopenia and Alzheimer's disease and believe that the prevention of muscle loss in older age will reduce the incidence of debilitating cognitive decline.

Promising membrane photobioreactor for continuous flow treatment of Low C/N wastewater: Treating process, community structure, and cooperation mechanism

Low carbon/nitrogen (C/N) wastewater treatment is an emerging issue for conventional treatment technologies. To achieve this goal, a novel membrane photobioreactor (MPBR), integrating microalgae consortium (MC) and activated sludge (AS) phases, was investigated. The separation of the MC and AS phases could improve the removal of pollutants in low C/N wastewater, which could achieve the rapid denitrogenation through NH4+-N assimilation in MC phase, and effectively reduce organic matter concentration in AS phase, resulting in better nutrient recovery, lower costs, and stable pH. The results in phase I showed that the pollutants, such as chemical oxygen demand (COD), ammonium (NH4+-N), and total phosphorus (TP), met the Environmental Quality Standards for Surface Water (GB3838–2002) by MPBR. The AS phase with low DO, which could enrich heterotrophic bacteria (e.g., Bacteroidetes vadinHA17, Spirochaeta and Ahniella) and nitrogen cycling bacteria (e.g., Mycobacterium, Bacillus and Ellin6067), could promote the removal of COD and NO3--N in the continuous effluent. Based on the co-occurrence pattern analysis, the main influencing factor of MC and AS phases was the reduction of COD, which also illustrated the synergistic removal of organic matter by the cooperative interaction of microalgae and heterotrophic bacteria. From a genetic perspective, the internal circulation mode also enhanced microbial nitrogen metabolism in the MPBRs, with higher abundances of nitrification- and denitrification-related functional genes in the MC phase, and higher abundances of nitrification, dissimilatory nitrate reduction, and denitrification genes in the AS phase. This study provided an experimental and theoretical basis for MPBR in low-C/N wastewater treatment.

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study.

Studies have shown that the gut microbiota is associated with male infertility (MI). However, their causal relationship and potential mediators need more evidence to prove. We aimed to investigate the causal relationship between the gut microbiome and MI and the potential mediating role of inflammatory cytokines from a genetic perspective through a Mendelian randomization approach. This study used data from genome-wide association studies of gut microbes (Mibiogen, n = 18, 340), inflammatory cytokines (NFBC1966, FYPCRS, FINRISK 1997 and 2002, n=13, 365), and male infertility (Finngen, n=120, 706) to perform two-way Mendelian randomization (MR), mediated MR, and multivariate MR(MVMR) analyses. In this study, the inverse variance weighting method was used as the primary analysis method, and other methods were used as supplementary analysis methods. In the present study, two gut microbes and two inflammatory cytokines were found to have a potential causal relationship with MI. Of the two gut microorganisms causally associated with male infertility, Anaerotruncus increased the risk of male infertility (odds ratio = 1.81, 95% confidence interval = 1.18-2.77, P = 0.0062), and Bacteroides decreased the risk of male infertility (odds ratio = 0.57, 95% confidence interval = 0.33-0.96, P = 0.0363). In addition, of the two inflammatory cytokines identified, hepatocyte growth factor(HGF) reduced the risk of male infertility (odds ratio = 0.50, 95% confidence interval = 0.35-0.71, P = 0.0001), Monocyte chemotactic protein 3 (MCP-3) increased the risk of male infertility (odds ratio = 1.28, 95% confidence interval = 1.03-1.61, P = 0.0039). Mediated MR analysis showed that HGF mediated the causal effect of Bacteroides on MI (mediated percentage 38.9%). Multivariate MR analyses suggest that HGF may be one of the pathways through which Bacteroides affects MI, with other unexplored pathways. The present study suggests a causal relationship between specific gut microbiota, inflammatory cytokines, and MI. In addition, HGF may mediate the relationship between Bacteroides and MI.

Understanding Pediatric Hemoglobinopathies: Epidemiology, Genetics, and Management Strategies

Children's hemoglobinopathies, such as thalassemias and sickle cell disease (SCD), present a diverse range of symptoms and complex genetic causes, which provide significant challenges for therapy. This website provides comprehensive information on the genetics, prevalence, and many treatment options available for baby hemoglobinopathies. Research in global epidemiology suggests that individuals suffer from a diverse array of ailments. Therefore, it is crucial to prioritize targeted screening programs and medicines. Understanding the fundamental concepts of basic genetics, such as autosomal recessive inheritance patterns and specific gene mutations, is crucial for developing precise diagnostic tools and personalized treatment strategies. Comprehensive management strategies encompass several approaches such as providing supportive care, utilizing pharmaceutical therapy, and implementing advanced techniques like gene therapy for treating disorders. Due to continuous research that enhances our comprehension of hemoglobinopathies, we should expect improved results and an enhanced standard of living for individuals affected by them. The purpose of this study is to enhance our comprehension of pediatric hemoglobinopathies and our approach to therapy by gathering the perspectives of epidemiology, genetics, and clinical practice.

Recent approaches towards characterization, genetic, and genomic perspectives of genus Lilium

Recent approaches towards characterization, genetic, and genomic perspectives of genus Lilium

The causal effects of immune cells on pancreatic cancer: A 2‑sample Mendelian randomization study.

Leveraging publicly available genetic datasets, we conducted a comprehensive 2-sample Mendelian randomization (MR) analysis to explore the causal links between 731 immunophenotypes and the risk of pancreatic cancer (PC). To ensure the robustness of our findings, extensive sensitivity analyses were performed, evaluating stability, heterogeneity, and potential horizontal pleiotropy. Our analysis pinpointed 24 immunophenotypes significantly associated with the risk of PC. Notably, phenotypes such as CD4+ CD8dim %leukocyte (OR = 0.852, 95% CI = 0.729-0.995, P = .0430) and HLA DR+ CD4+ AC (OR = 0.933, 95% CI = 0.883-0.986) in TBNK were inversely correlated with PC risk. Conversely, phenotypes like CD28 on CD45RA- CD4 non-Treg (OR = 1.155, 95% CI = 1.028-1.297, P = .016) and CD25 on activated Treg (OR = 1.180, 95% CI = 1.014-1.374, P = .032) in Treg cells, among others, exhibited a positive correlation. These insights offer a valuable genetic perspective that could guide future clinical research in this area.

Inflammatory cytokine profiles in erectile dysfunction: a bidirectional Mendelian randomization.

Inflammatory cytokines (ICs) play an important role in erectile dysfunction (ED). Previous studies have demonstrated that most ED patients have high levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). The causality between 41 ICs and ED is investigated using the Mendelian randomization (MR) approach. Single nucleotide polymorphisms (SNPs) exposure data of 41 ICs came from a genome-wide association study (GWAS) of 8293 subjects. At the same time, the FINNGEN R9 database provided the ED outcome data containing 2205 ED patients and 164104 controls. MR-Egger (ME), inverse variance weighting (IVW), and weighted median (WM) were applied to conduct the MR study and IVW was taken as the main criterion. From a genetic perspective, the increase of interferon-inducible protein-10 (IP-10) level significantly increased the risk of ED (P=0.043, odds ratio (OR)=1.269, 95% confidence interval (95%CI): 1.007-1.600), while the increase of interleukin-1 receptor antagonist (IL-1RA) markedly decreased the risk of ED (P=0.037, OR=0.768, 95%CI: 0.600-0.984). Meanwhile, IP-10 (p=0.099) and IL-1RA (p=0.135) failed to demonstrate causality in reverse MR analysis. Changes in ICs levels will significantly affect the risk of ED, especially IP-10 as a risk component for ED and IL-1RA as a protective component for ED. In the future, we can achieve targeted treatment and prevention of ED by intervening with specific inflammatory factors.

Integrative analysis of proteomics and lipidomic profiles reveal the fat deposition and meat quality in Duroc × Guangdong small spotted pig.

This study aims to explore the important factors affecting the characteristics of different parts of pork. Lipidomics and proteomics methods were used to analyze DAL (differential lipids) and DAPs (differential proteins) in five different parts (longissimus dorsi, belly meat, loin, forelegs and buttocks) of Duhua pig (Duroc × Guangdong small spotted pig), to identify potential pathways affecting meat quality, investigating fat deposition in pork and its lipid-protein interactions. The results show that TG (triglyceride) is the lipid subclass with the highest proportion in muscle, and the pathway with the most significantly enriched lipids is GP. DAP clustered on several GO terms closely related to lipid metabolism and lipogenesis (lipid binding, lipid metabolism, lipid transport, and lipid regulation). In KEGG analysis, there are two main DAP aggregation pathways related to lipid metabolism, namely Fatty acid degradation and oxidative phosphorylation. In PPI analysis, we screened out 31 core proteins, among which NDUFA6, NDUFA9 and ACO2 are the most critical. PC (phosphatidylcholine) is regulated by SNX5, THBS1, ANXA7, TPP1, CAVIN2, and VDAC2 in the phospholipid binding pathway. TG is regulated by AUH/HADH/ACADM/ACADL/HADHA in the lipid oxidation and lipid modification pathways. Potential biomarkers are rich in SFA, MUFA and PUFA respectively, the amounts of SFA, MUFA and PUFA in the lipid measurement results are consistent with the up- and down-regulation of potential biomarker lipids. This study clarified the differences in protein and lipid compositions in different parts of Duhua pigs and provided data support for revealing the interactions between pork lipids and proteins. These findings provide contributions to the study of intramuscular fat deposition in pork from a genetic and nutritional perspective.