Trio-based genome sequencing identifies candidate causal genes in lifelong premature ejaculation.
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ABSTRACT:
SUBMITTER: Wang DQ
PROVIDER: S-EPMC8152429 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Given that sexual behavior is usually pleasurable and highly rewarding, it is surprising that there is as yet no known research to empirically assess how premature ejaculation (PE) patients respond to the rewarding aspect of sexual behavior. This study was designed to address this issue by evaluating how these men respond to the anticipation and hedonic experience of sexual rewards in comparison to non-sexual rewards. Thirty lifelong PE patients and thirty healthy controls (HCs) performed the incentive delay task manipulating both erotic and monetary rewards. Compared to HCs, lifelong PE patients exhibited significantly faster RTs to erotic cues than to monetary cues during reward anticipation. Meanwhile, hedonic experience ratings after obtaining the actual reward showed that erotic rewards were rated as more pleasant than monetary rewards only by lifelong PE patients, which was driven by a decreased sensitivity to experienced monetary rewards in lifelong PE patients compared to HCs. These findings indicate the existence of dysfunctional reward processing in lifelong PE patients, which is characterized by increased incentive motivation elicited by sexual cues and reduced hedonic impact of nonsexual rewards. This study may offer an insightful clue regarding how PE is related to the abnormal regulation of the rewarding aspect of sexual behavior.
| S-EPMC10579392 | biostudies-literature
Project description:Premature ejaculation (PE) is the most common male sexual dysfunction. The brain disturbances that cause this disorder remain poorly understood. This study aimed to investigate how the morphology of cortical and subcortical brain structures differed in PE, how these morphologic differences were associated with severity measures of PE, such as intravaginal ejaculatory latency time (IELT), and how these cortical and subcortical structures were causally connected through mediation analysis. Anatomical MRI scans were acquired from 39 male participants, 23 with PE (28.78 ± 4.32 years), and 16 without PE (27.88 ± 3.65 years). We used a subcortical analysis package within FSL to perform subcortical shape segmentation and statistical analysis. The PE group was compared with the normal control (NC) group in the shapes of 15 subcortical structures with general linear models [p < 0.05, family-wise error (FWE)-corrected]. We analyzed the cortical complexity revealed by the gyrification index using the Computational Anatomy Toolbox (CAT12). Vertex-wise shape analyses revealed outward shape deformations (expansions) in the left hippocampus and bilateral thalamus. Gyrification index analyses revealed that the right orbital frontal cortex and the right nucleus accumbens had greater complexity in PE patients. The shape deformations were positively correlated with the IELTs in the NC group, while this relationship was interrupted in the PE group. PE is associated with outward deformations of the subcortical surfaces and more complexity of the cortical structures. These morphological differences may be the basis of the brain functional alterations underlying PE.
| S-EPMC7387657 | biostudies-literature
Project description:ObjectiveThis study aimed to develop an effective support vector machine (SVM) classifier based on the multi-modal data for detecting the main brain networks involved in group separation of premature ejaculation (PE).MethodsA total of fifty-two patients with lifelong PE and 36 matched healthy controls were enrolled in this study. Structural MRI data, functional MRI data, and diffusion tensor imaging (DTI) data were used to process SPM12, DPABI4.5, and PANDA, respectively. A total of 12,735 features were reduced by the Mann-Whitney U test. The resilience nets method was further used to select features.ResultsFinally, 36 features (3 structural MRI, 7 functional MRI, and 26 DTI) were chosen in the training dataset. We got the best SVM model with an accuracy of 97.5% and an area under the curve (AUC) of 0.986 in the training dataset as well as an accuracy of 91.4% and an AUC of 0.966 in the testing dataset.ConclusionOur findings showed that the majority of the brain abnormalities for the classification was located within or across several networks. This study may contribute to the neural mechanisms of PE and provide new insights into the pathophysiology of patients with lifelong PE.
| S-EPMC9357875 | biostudies-literature
Project description:PurposeGenetic factors play an indispensable role in the pathogenesis of lifelong premature ejaculation (LPE). The susceptibility genes/SNPs that have been discovered are very limited and can only explain part of the genetic effects of LPE. Therefore, discovering more genetic polymorphisms associated with the occurrence and development of LPE will help reveal the pathogenesis of LPE.Materials and methodsWe conducted a genome-wide association study of LPE in 486 Chinese male Han people (cases and controls). We used Gene Titan multi-channel instrument and Axiom Analysis Suite 6.0 software for genotyping. Imputation was performed by IMPUTE2 software and the 1000 Genomes Project (Phase3) was used as reference for haplotype. Finally, logistic regression analysis was performed on all loci that passed the quality control. The odds ratio and 95% confidence interval were calculated to determine the association between each SNPs and Chinese male Han population LPE risk.ResultsThe results showed that a total of 33 genetic variants in 13 genes (LACTBL1, SSBP3, ACOT11, LINC02486, TMEM154, LINC01098, NONE, HCG27, HLA-C, TNFSF8, TNC, FAM53B, SULF2) have a suggestively significant genome-wide association with LPE risk (p<5×10-6).ConclusionsThis study is the first to conduct a GWAS on LPE in Chinese male Han population 33 genetic polymorphisms have a suggestive genome-wide association with LPE risk. This study have provided data supplement for the genetic loci of LPE risk, and laid a scientific foundation for the pathogenesis and the targeted therapy of LPE.
| S-EPMC8987137 | biostudies-literature
Project description:BackgroundGenetic causes that lead to spermatogenetic failure in patients with nonobstructive azoospermia (NOA) have not been yet completely established.ObjectiveTo identify low-frequency NOA-associated single nucleotide variants (SNVs) using whole-genome sequencing (WGS).Materials and methodsMen with various types of NOA (n = 39), including samples that had been previously tested with whole-exome sequencing (WES; n = 6) and did not result in diagnostic conclusions. Variants were annotated using the Ensembl Variant Effect Predictor, utilizing frequencies from GnomAD and other databases to provide clinically relevant information (ClinVar), conservation scores (phyloP), and effect predictions (i.e., MutationTaster). Structural protein modeling was also performed.ResultsUsing WGS, we revealed potential NOA-associated SNVs, such as: TKTL1, IGSF1, ZFPM2, VCX3A (novel disease causing variants), ESX1, TEX13A, TEX14, DNAH1, FANCM, QRICH2, FSIP2, USP9Y, PMFBP1, MEI1, PIWIL1, WDR66, ZFX, KCND1, KIAA1210, DHRSX, ZMYM3, FAM47C, FANCB, FAM50B (genes previously known to be associated with infertility) and ALG13, BEND2, BRWD3, DDX53, TAF4, FAM47B, FAM9B, FAM9C, MAGEB6, MAP3K15, RBMXL3, SSX3 and FMR1NB genes, which may be involved in spermatogenesis.Discussion and conclusionIn this study, we identified novel potential candidate NOA-associated genes in 29 individuals out of 39 azoospermic males. Note that in 5 out of 6 patients subjected previously to WES analysis, which did not disclose potentially causative variants, the WGS analysis was successful with NOA-associated gene findings.
| S-EPMC9826517 | biostudies-literature
Project description:INTRODUCTION:Premature ejaculation (PE) is widely regarded as one of the most common sexual dysfunctions in men. The neurobiogenesis of PE is complex and involves the serotoninergic (5-HT) system. AIM:In this study, we investigated whether polymorphisms in the tryptophan hydroxylase 2 (TPH2) gene were associated with lifelong PE (LPE). METHODS:A total of 121 men diagnosed with LPE were recruited from our outpatient clinics and 94 healthy controls from the health examination center. Intravaginal ejaculation latency time (IELT) was measured using a stopwatch. The PE diagnostic tool (PEDT) data were collected at the same time. All subjects with LPE and healthy controls were genotyped for polymorphisms in the TPH2 gene. Allele and genotype frequencies of single-nucleotide polymorphisms (SNPs) were compared between the patients and controls. MAIN OUTCOME MEASURE:The main outcome measures are IELT and PEDT to diagnose LPE. The association of LPE with TPH2 gene polymorphisms in these areas was investigated. RESULTS:The IELT, PEDT scores, and education levels in the LPE group were significantly different from those in the control group. Statistically significant differences were found in the SNPs of SNV019 and rs4290270. The frequencies of the G allele and G/A genotype of SNV019 were significantly higher in the patients with LPE than in the controls (P = .045 and .037, respectively). The A allele and A/A genotype of rs4290270 were more frequent in the patients with LPE than in the controls (P = .037 and .049, respectively). In the dominant model of inheritance, the SNV019 polymorphism in the patients with LPE was significantly different from that in the controls (odds ratio [95% confidence interval] = 2.936 [1.066-8.084], P = .037). In men with LPE, there was no statistically significant association between genotype and median IELT. CONCLUSION:The SNPs SNV019 and rs4290270 of the TPH2 gene seemed to be associated with LPE in the Han population. Men with the A allele of SNV019 or the T allele of rs4290270 may be less likely to suffer from LPE. Fu X, Zhang X, Jiang T, et al. Association Between Lifelong Premature Ejaculation and Polymorphism of Tryptophan Hydroxylase 2 Gene in the Han Population. Sex Med 2020;8:223-229.
| S-EPMC7261684 | biostudies-literature
Project description:BackgroundLifelong premature ejaculation (LPE) is one of the most common ejaculatory dysfunctions in men. The serotonin (5-HT) synthesis rate-limiting enzyme (TPH2) and receptor (HTR1A) in the 5-HT regulatory system may play a key role in the pathogenesis of LPE. However, there are few studies on the effects of TPH2 and HTR1A polymorphisms on LPE risk. We speculated that TPH2 and HTR1A polymorphisms may affect the occurrence and development of LPE in the Chinese Han population.MethodsIn this study, 91 patients with LPE and 362 normal controls aged 18 to 64 years were enrolled in the male urology department of Hainan General Hospital in China from January 2016 to December 2018. The SNPs in HTR1A and TPH2, which are related to 5-HT regulation, were selected as indexes to genotype the collected blood samples of participants. Logistic regression was used to analyze the correlation between SNPs of HTR1A and TPH2 with LPE susceptibility, as well as the relationship with leptin, 5-HT and folic acid levels.ResultsThe results revealed that HTR1A-rs6295 increased LPE risk in recessive model. Rs11178996 in TPH2 significantly reduced susceptibility to LPE in allelic (odds ratio (OR) = 0.68, 95% confidence interval (95% CI) = 0.49-0.96, p = 0.027), codominant (OR = 0.58, 95% CI = 0.35-0.98, p = 0.040), dominant (OR = 0.58, 95% CI = 0.36-0.92, p = 0.020), and additive (OR = 0.71, 95% CI = 0.52-0.98, p = 0.039) models. Grs11179041Trs10879352 could reduce the risk of LPE (OR = 0.44, 95% CI = 0.22-0.90, p = 0.024) by haplotype analysis.ConclusionHTR1A-rs6295 and TPH2-rs11178996 are associated with LPE risk in the Chinese Han population based on the finding of this study.
| S-EPMC10170821 | biostudies-literature
Project description:BackgroundLifelong premature ejaculation (LPE) is a rare sexual condition believed to be caused by genetic neurobiological disorders. In the field of LPE, 2 main types of research have been conducted: direct genetic research and pharmacotherapeutic interference of neurotransmitter systems that can relieve the symptoms of LPE in male patients.ObjectiveWe aim to provide an overview of studies on neurotransmitter systems as the pathophysiological cause of LPE by investigating direct genetic research or pharmacotherapeutic interference that relieves the main symptom of LPE in male patients.MethodsThis scoping review will use the PRISMA-ScR tool (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). In addition, this study will use a peer-reviewed search strategy. Systematic searches will be conducted using 5 scientific databases (Cochrane Database of Systematic Reviews, PubMed or MEDLINE, Cumulative Index to Nursing and Allied Health Literature [CINAHL], EMBASE, and Epistemonikos). Additionally, pragmatic searches for relevant information in gray literature databases will be performed. Two reviewers will independently include relevant studies in a 2-stage selection strategy. Finally, data will be extracted from the studies and charted to summarize relevant study characteristics and key findings.ResultsAs of July 2022, we completed the preliminary searches according to the PRESS 2015 guidelines and started to determine the final search terms that we will use in all selected 5 scientific databases.ConclusionsThis scoping review protocol is the first to focus on neurotransmitter pathways in LPE by combining the results from the genetic and pharmacotherapy studies. The results could help identify potential research gaps or target candidate proteins and neurotransmitter pathways in LPE for further genetic research.Trial registrationOpen Science Framework 10.17605/OSF.IO/JUQSD; https://osf.io/juqsd.International registered report identifier (irrid)PRR1-10.2196/41301.
| S-EPMC10131874 | biostudies-literature
Project description: Not available
| S-EPMC5753546 | biostudies-literature
Project description:We are performing whole-genome sequencing of families with autism spectrum disorder (ASD) to build a resource (MSSNG) for subcategorizing the phenotypes and underlying genetic factors involved. Here we report sequencing of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible on a cloud platform and through a controlled-access internet portal. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertions and deletions or copy number variations per ASD subject. We identified 18 new candidate ASD-risk genes and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (P = 6 × 10-4). In 294 of 2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried copy number variations and/or chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD.
| S-EPMC5501701 | biostudies-literature