UNASSIGNED: Observational clinical studies suggest an association between dilated cardiomyopathy (DCM) and various factors including titin, cardiac troponin I (CTnI), desmocollin-2, the perinatal period, alcoholism, Behçet\'s disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency. The causal nature of these associations remains uncertain. This study aims to explore these correlations using the Mendelian randomization (MR) approach.
UNASSIGNED: To investigate the etiology of DCM through Mendelian randomization analysis.
UNASSIGNED: Data mining was conducted in genome-wide association study databases, focusing on variant target proteins (titin, CTnI, desmocollin-2), the perinatal period, alcoholism, Behçet\'s disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, and renal insufficiency, with DCM as the outcome. The analysis employed various regression models, namely, the inverse-variance weighted (IVW), MR-Egger, simple mode, weighted median, and weighted mode methods.
UNASSIGNED: The IVW results showed a correlation between titin protein and DCM, identifying titin as a protective factor [OR = 0.856, 95% CI (0.744-0.985), P = 0.030]. CTnI protein correlated with DCM, marking it as a risk factor [OR = 1.204, 95% CI (1.010-1.436), P = 0.040]. Desmocollin-2 also correlated with DCM and was recognized as a risk factor [OR = 1.309, 95% CI (1.085-1.579), P = 0.005]. However, no causal relationship was found between the perinatal period, alcoholism, Behçet\'s disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, renal insufficiency, and DCM (P > 0.05). The MR-Egger intercept test indicated no pleiotropy (P > 0.05), affirming the effectiveness of Mendelian randomization in causal inference.
UNASSIGNED: Titin, CTnI, and desmocollin-2 proteins were identified as independent risk factors for DCM. Contrasting with previous observational studies, no causal relationship was observed between DCM and the perinatal period, alcoholism, Behçet\'s disease, systemic lupus erythematosus, hyperthyroidism and thyrotoxicosis, hypothyroidism, carnitine metabolic disorder, or renal insufficiency.

UNASSIGNED: Avocado (Persea americana) is a highly nutritious fruit gaining worldwide popularity. However, its cultivation is currently reliant on a limited number of cultivars with restricted genetic diversity. This study aims to investigate the genetic diversity and population structure of avocado germplasm and identify genetic loci associated with key fruit quality traits that influence customer preference.
UNASSIGNED: A diversity panel of 110 avocado accessions was analyzed using 4,706 high-quality single nucleotide polymorphisms (SNPs). Genetic diversity and population structure were analyzed using pairwise FST, AMOVA, admixture analysis, and phylogenetic analysis. Genome-wide association studies (GWAS) were conducted targeting nine fruit quality traits using two models: General Linear Model (GLM) with Principal Component Analysis (PCA) and Mixed Linear Model (MLM) with PCA and kinship (PCA + K).
UNASSIGNED: The analysis revealed three distinct populations corresponding to the three avocado ecotypes: Guatemalan, West Indian, and Mexican. Phylogenetic analysis indicated a closer relationship between the Guatemalan and West Indian races compared to the Mexican race in our Florida germplasm collection. GWAS led to identification of 12 markers within 11 genomic regions significantly associated with fruit quality traits such as fruit color, shape, taste, and skin texture. These markers explained between 14.84% to 43.96% of the phenotypic variance, with an average of 24.63%. Annotation of these genomic regions unveiled candidate genes potentially responsible for controlling these traits.
UNASSIGNED: The findings enhance our understanding of genetic diversity and population structure in avocado germplasm. The identified genetic loci provide valuable insights into the genetic basis of fruit quality traits, aiding breeding programs in developing improved avocado cultivars. Marker-assisted selection can accelerate the development of new varieties, promoting a more diverse and resilient avocado market.

BACKGROUND: Telomere shortening and epigenetic modifications are key factors in aging and hematologic diseases. This study investigates the relationship of telomere length and epigenetic age acceleration (EAA) with hematologic cancers, blood cells, and biochemical markers through the epigenetic clocks.
METHODS: This study primarily utilizes genome-wide association studies of populations of European descent as instrumental variables, exploring the causal relationships between exposures and outcomes through a bidirectional two-sample Mendelian randomization (MR) approach. MR techniques include inverse variance weighted (IVW), MR Egger, and weighted median modes. Heterogeneity and pleiotropy in MR are assessed using Cochran\'s Q test and the MR Egger intercept, with the robustness of the conclusions further validated by multivariable MR (MVMR).
RESULTS: Our research shows that longer telomere lengths significantly increase the risk of multiple myeloma, leukemia, and lymphoma (OR > 1, P < 0.05) and establish a causal relationship between telomere length and red blood cell indices such as RBC (OR = 1.121, PIVW = 0.034), MCH (OR = 0.801, PIVW = 2.046e-06), MCV (OR = 0.801, PIVW = 0.001), and MCHC (OR = 0.813, PIVW = 0.002). Additionally, MVMR analysis revealed an association between DNA methylation PhenoAge acceleration and alkaline phosphatase (OR = 1.026, PIVW = 0.007).
CONCLUSIONS: The study clarifies the relationships between telomere length, EAA, and hematological malignancies, further emphasizing the prognostic significance of telomere length and EAA. This deepens our understanding of the pathogenesis of hematological diseases, which can inform risk assessment and therapeutic strategies.

BACKGROUND: Juvenile Idiopathic Arthritis (JIA) is a complex autoimmune disease and the most common chronic rheumatological disease affecting children under the age of 16. The etiology of JIA remains poorly understood, but evidence suggests a significant genetic predisposition.
METHODS: We analyzed a Swedish cohort of 329 JIA patients and 728 healthy adult controls using the Illumina OmniExpress array for genotyping. HLA alleles were imputed from GWAS data using the SNP2HLA algorithm.
RESULTS: Case-control analysis yielded 12 SNPs with genome-wide significant association to JIA, all located on chromosome 6 within the MHC class II gene region. Notably, the top SNP (rs28421666) was located adjacent to HLA-DQA1 and HLA-DRB1. HLA-DRB1*08:01, HLA-DQA1*04:01, and HLA-DQB1*04:02 were the haplotypes most strongly associated with an increased risk of JIA in the overall cohort. When analyzing disease specific subtypes, these alleles were associated with oligoarthritis and RF-negative polyarthritis. Within the complex linkage disequilibrium of the HLA-DRB1-DQA1-DQB1 haplotype, our analysis suggests that HLA-DRB1*08 might be the primary allele linked to JIA susceptibility. The HLA-DRB1*11 allele group was also independently associated with JIA and specifically enriched in the oligoarthritis patient group. Additionally, our study revealed a significant correlation between antinuclear antibody (ANA) positivity and specific HLA alleles. The ANA-positive JIA group showed stronger associations with the HLA-DRB1-DQA1-DQB1 haplotype, HLA-DRB1*11, and HLA-DPB1*02, suggesting a potential connection between genetic factors and ANA production in JIA. Furthermore, logistic regression analysis reaffirmed the effects of HLA alleles, female sex, and lower age at onset on ANA positivity.
CONCLUSIONS: This study identified distinct genetic associations between HLA alleles and JIA subtypes, particularly in ANA-positive patients. These findings contribute to a better understanding of the genetic basis of JIA and provide insights into the genetic control of autoantibody production in ANA-positive JIA patients. This may inform future classification and personalized treatment approaches for JIA, ultimately improving patient outcomes and management of this disease.

Hypertrophic scar (HS) results from burns or trauma, causing aesthetic and functional issues. However, observational studies have linked inflammatory cytokines to HS, but the causal pathways involved are unclear. We aimed to determine how circulating inflammatory cytokines contribute to HS formation. Two-sample Mendelian randomization (MR) was used to identify genetic variants associated with hypertrophic scar in a comprehensive, publicly available genome-wide association study (GWAS) involving 766 patients and 207,482 controls of European descent. Additionally, data on 91 plasma proteins were drawn from a GWAS summary involving 14,824 healthy participants. Causal relationships between exposures and outcomes were investigated primarily using the inverse variance weighted (IVW) method. Furthermore, a suite of sensitivity analyses, including MR‒Egger and weighted median approaches, were concurrently employed to fortify the robustness of the conclusive findings. Finally, reverse MR analysis was conducted to evaluate the plausibility of reverse causation between hypertrophic scar and the cytokines identified in our study. In inflammatory cytokines, there was evidence of inverse associations of osteoprotegerin(OPG) levels(OR = 0.59, 95% CI = 0.41 ∼ 0.85, p = 0.01), and leukemia inhibitory factor(LIF) levels(OR = 0.51, 95% CI = 0.32 ∼ 0.82, p = 0.01) are a nominally negative association with hypertrophic scar risk, while CUB domain-domain-containing protein 1(CDCP1) level(OR = 0.59, 95% CI = 0.41 ∼ 0.85, p = 0.01) glial cell line-derived neurotrophic factor(GDNF) levels(OR = 1.42, 95% CI = 1.03 ∼ 1.96, p = 0.01) and programmed cell death 1 ligand 1(PD-L1) levels(OR = 1.47, 95% CI = 1.92 ∼ 2.11, p = 0.04) showed a positive association with hypertrophic scar risk. These associations were similar in the sensitivity analyses. According to our MR findings, OPG and LIF have a protective effect on hypertrophic scar, while CDCP1, GDNF, and PD-L1 have a risk-increasing effect on Hypertrophic scar. Our study adds to the current knowledge on the role of specific inflammatory biomarker pathways in hypertrophic scar. Further validation is needed to assess the potential of these cytokines as pharmacological or lifestyle targets for hypertrophic scar prevention and treatment.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease characterized by the accumulation of aggregated tau proteins in astrocytes, neurons, and oligodendrocytes. Previous genome-wide association studies for PSP were based on genotype array, therefore, were inadequate for the analysis of rare variants as well as larger mutations, such as small insertions/deletions (indels) and structural variants (SVs).
METHODS: In this study, we performed whole genome sequencing (WGS) and conducted association analysis for single nucleotide variants (SNVs), indels, and SVs, in a cohort of 1,718 cases and 2,944 controls of European ancestry. Of the 1,718 PSP individuals, 1,441 were autopsy-confirmed and 277 were clinically diagnosed.
RESULTS: Our analysis of common SNVs and indels confirmed known genetic loci at MAPT, MOBP, STX6, SLCO1A2, DUSP10, and SP1, and further uncovered novel signals in APOE, FCHO1/MAP1S, KIF13A, TRIM24, TNXB, and ELOVL1. Notably, in contrast to Alzheimer\'s disease (AD), we observed the APOE ε2 allele to be the risk allele in PSP. Analysis of rare SNVs and indels identified significant association in ZNF592 and further gene network analysis identified a module of neuronal genes dysregulated in PSP. Moreover, seven common SVs associated with PSP were observed in the H1/H2 haplotype region (17q21.31) and other loci, including IGH, PCMT1, CYP2A13, and SMCP. In the H1/H2 haplotype region, there is a burden of rare deletions and duplications (P = 6.73 × 10-3) in PSP.
CONCLUSIONS: Through WGS, we significantly enhanced our understanding of the genetic basis of PSP, providing new targets for exploring disease mechanisms and therapeutic interventions.

UNASSIGNED: Breeding rice with drought tolerance for harsh environments is crucial for agricultural sustainability. Understanding the genetic underpinnings of drought tolerance is vital for developing resilient rice varieties. Genome-wide association studies (GWAS) have emerged as pivotal tools in unravelling the complex genetic architecture of traits like drought tolerance, capitalizing on the natural genetic diversity within rice germplasm collections.
UNASSIGNED: In this study, a comprehensive panel of 210 rice varieties was phenotyped over ten days in controlled conditions, subjected to simulated drought stress using 20% PEG 6000 in petri dishes. Throughout the stress period, crucial traits such as germination percentage (GP), germination rate index (GRI), mean germination time (MGT), and seedling percentage (SP) were meticulously monitored.
UNASSIGNED: The GWAS analysis uncovered a total of 38 QTLs associated with drought tolerance traits, including novel loci like qMGT-5.2, qSP-3, qSP7.2, and qGP-5.2. Additionally, RNA-seq analysis identified ten genes with significant expression differences under drought stress conditions. Notably, haplotype analysis pinpointed elite haplotypes in specific genes linked to heightened drought tolerance.
UNASSIGNED: Overall, this study underscores the importance of GWAS in validating known genes while unearthing novel loci to enrich the genetic resources for enhancing drought tolerance in rice breeding programs.

BACKGROUND: Atrial fibrillation (AF), the most common atrial arrhythmia, presents with varied clinical manifestations. Despite the identification of genetic loci associated with AF, particularly in specific populations, research within Asian ethnicities remains limited. In this study we aimed to develop predictive models for AF using AF-associated single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS) on a substantial cohort of Taiwanese individuals, to evaluate the predictive efficacy of the model.
METHODS: There were 75,121 subjects, that included 5694 AF patients and 69,427 normal control subjects with GWAS data, and we merged polygenic risk scores from AF-associated SNPs with phenome-wide association study-derived risk factors. Advanced statistical and machine learning techniques were used to develop and evaluate AF predictive models for discrimination and calibration.
RESULTS: The study identified the top 30 significant SNPs associated with AF, predominantly on chromosomes 10 and 16, implicating genes like NEURL1, SH3PXD2A, INA, NT5C2, STN1, and ZFHX3. Notably, INA, NT5C2, and STN1 were newly linked to AF. The GWAS predictive power using polygenic risk score-continuous shrinkage analysis for AF exhibited an area under the curve of 0.600 (P < 0.001), which improved to 0.855 (P < 0.001) after adjusting for age and sex. Phenome-wide association study analysis showed the top 10 diseases associated with these genes were circulatory system diseases.
CONCLUSIONS: Integrating genetic and phenotypic data enhanced the accuracy and clinical relevance of AF predictive models. The findings suggest promise for refining AF risk assessment, enabling personalized interventions, and reducing AF-related morbidity and mortality burdens.

OBJECTIVE: To analyze genome-wide studies devoted to polymorphisms of factors of anterior abdominal wall hernias, to study the association of the most common polymorphism In Russian population.
METHODS: Searching for literature data was carried out in the RSCI and PubMed databases. We enrolled national and foreign reports. The study on Russian population included 577 people.
RESULTS: We found 5 genome-wide studies performed by foreign authors. We identified the loci responsible for genetic predisposition to inguinal hernias: WT1, EFEMP1, EBF2 and ADAMTS6. The Japanese scientists revealed an important role of loci TGFB2, RNA5SP214/VGLL2, LOC646588, HMCN2, ATP5F1CP1/CDKN3. In other studies, loci 1q41 (ZC3H11B), 2p16.1 (EFEMP1), 6p22.1 (MHC region), 7q33 (CALD1) and 11p13 (WT1) determined different hernias. The EFEMP1 gene polymorphism was among genes most associated with anterior abdominal wall hernias in all studies. Analysis of this polymorphism In Russian population revealed significant association with anterior abdominal wall hernias.
CONCLUSIONS: The obtained data on target correction of DNA chains can significantly reduce the incidence of anterior abdominal wall hernias. In turn, this will significantly reduce the cost of surgical treatment and risk of complications with recurrences of hernias. Moreover, identifying the most associated polymorphisms may be valuable to determine the most appropriate surgical treatment.
UNASSIGNED: Провести обзор данных литературы на тему широкогеномных исследований ассоциаций полиморфизма факторов образования грыж передней брюшной стенки, изучить ассоциацию наиболее встречаемого полиморфизма на русской популяции.
UNASSIGNED: Поиск данных литературы, обозреваемых в данной статье, проводился в базах данных РИНЦ и PubMed. Были использованы как отечественные, так и зарубежные источники. Исследование на русской популяции проведено у 577 человек.
UNASSIGNED: В результате анализа найдено 5 широгеномных исследований, выполненных зарубежными авторами. При изучении этих статей установлены локусы, ответственные за генетическую предрасположенность к образованию паховых грыж: WT1, EFEMP1, EBF2 и ADAMTS6. В исследовании японских ученых важную роль играли локусы TGFB2, RNA5SP214/VGLL2, LOC646588, HMCN2, ATP5F1CP1/CDKN3. В других трудах — локусы 1q41 (ZC3H11B), 2p16.1 (EFEMP1), 6p22.1 (MHC region), 7q33 (CALD1) и 11p13 (WT1) детерминировали в развитии разных типов грыж. Полиморфизм гена EFEMP1 был в числе максимально ассоциированных генов с грыжами передней брюшной стенки во всех найденных исследованиях. При изучении ассоциации этого полиморфизма в русской популяции также была выявлена достоверная связь с грыжами передней брюшной стенки.
UNASSIGNED: Применение полученных данных в рамках точечной коррекции ДНК-цепей может позволить существенно снизить образование грыж передней брюшной стенки, что сократит расходы на оперативное лечение, а также снизит риск осложнений и частоту рецидива грыж. Кроме того, выявление вариантов максимально ассоциированного полиморфизма может помочь хирургу в определении тактики оперативного лечения.

UNASSIGNED: The prefrontal cortex (PFC) has been strongly implicated in the pathophysiology of schizophrenia. Here, we combined high-resolution single-nuclei RNA sequencing data from the human PFC with large-scale genomic data for schizophrenia to identify constituent cell populations likely to mediate genetic liability to the disorder.
UNASSIGNED: Gene expression specificity values were calculated from a single-nuclei RNA sequencing dataset comprising 84 cell populations from the human PFC, spanning gestation to adulthood. Enrichment of schizophrenia common variant liability and burden of rare protein-truncating coding variants were tested in genes with high expression specificity for each cell type. We also explored schizophrenia common variant associations in relation to gene expression across the developmental trajectory of implicated neurons.
UNASSIGNED: Common risk variation for schizophrenia was prominently enriched in genes with high expression specificity for a population of mature layer 4 glutamatergic neurons emerging in infancy. Common variant liability to schizophrenia increased along the developmental trajectory of this neuronal population. Fine-mapped genes at schizophrenia genome-wide association study risk loci had significantly higher expression specificity than other genes in these neurons and in a population of layer 5/6 glutamatergic neurons. People with schizophrenia had a higher rate of rare protein-truncating coding variants in genes expressed by cells of the PFC than control individuals, but no cell population was significantly enriched above this background rate.
UNASSIGNED: We identified a population of layer 4 glutamatergic PFC neurons likely to be particularly affected by common variant genetic risk for schizophrenia, which may contribute to disturbances in thalamocortical connectivity in the condition.
The prefrontal cortex (PFC) has been strongly implicated in the underlying biology of schizophrenia. We tested whether specific cell populations within the PFC preferentially express genes that increase risk for the disorder. We found that a particular type of PFC neuron prominently expresses genes associated with schizophrenia, suggesting its involvement in the condition.