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Causal association between vitamin D and gestational diabetes mellitus: a two-sample Mendelian randomization study.

BACKGROUND: Previous articles on the relationship between vitamin D and gestational diabetes mellitus (GDM) were inconsistent. Their relationship has been observed primarily through observational studies, and the causality of this association has not been established. METHODS: A two-sample Mendelian randomization (MR) research was conducted to test the causal association between vitamin D and GDM, utilizing publically available statistics from genome-wide association studies (GWAS). This study obtained genetic variants from GWAS including vitamin D (N = 373,045,10,783,672 Single Nucleotide Po

Distinct genetic signals at the FGF21 locus complicate studies of FGF21's role in diet regulation using human cohort data.

OBJECTIVES: Experimental and genetic studies suggest that fibroblast growth factor 21 (FGF21) modulates macronutrient and alcohol preferences, but evidence of such regulation in humans remains scarce. To address this gap in translation, we aimed to map the relationships between plasma FGF21 levels, FGF21 genetic variation and habitual macronutrient intake in a large human population. METHODS: We fine-mapped and performed colocalization of the FGF21 genetic region in GWAS summary statistics of plasma FGF21 levels and macronutrient intake. UK Biobank data were used to investigate the associatio

Juvenile idiopathic arthritis and primary ovarian failure: a two-sample Mendelian randomization analysis in a mixed-gender cohort.

BACKGROUND: The causal relationship between juvenile idiopathic arthritis (JIA) and primary ovarian failure (POF) remains uncertain. To elucidate this relationship, we employed a two-sample Mendelian randomization analysis. METHODS: The single nucleotide polymorphisms (SNPs) associated with JIA were obtained from a previously published genome-wide association study (GWAS), while the pooled data for POF originated from the FinnGen consortium. The study populations consisted exclusively of individuals of European descent. In our Mendelian randomization analysis, we performed inverse-variance we…

Множественный склероз Полигенный риск не обогащается в Three Множественные семьи в сопоставлении с демографическими случаями.

Множественный склероз (MS) — сложное неврологическое и аутоиммунное заболевание с установленным генетическим компонентом. Семьи с множественными случаями MS встречаются редко, но это происходит. Мы гипотезуем, что многодетные семьи могут иметь повышенный полигенный риск для MS. В ходе этой работы мы определили, обогащается ли полигенный риск для НР в многодетных семьях по сравнению с когортой контроля за конкретными случаями. Используя результаты крупнейшего исследования, проведенного в рамках ассоциации по геному MS, мы рассчитали взвешенный показатель полигенного риска (wPRS) для MS. Мы прим

Совпадение в аннотации оригинала
Multiple sclerosis (MS) is a complex neurological and autoimmune disease with an established genetic component. Families with multiple cases … n multicase families in comparison to a case-control cohort. Using the findings from the largest MS genome-wide association study, we calculated a weighted polygenic risk score (wPRS) for MS. We applied this wPRS to study a population-based MS case-control cohort (3,252 people with MS and 5,725 controls) and three multicase MS families (9 individuals with MS, 10 unaffected fam …

Association of rs2282679 polymorphism in vitamin D binding protein gene (GC) with the risk of vitamin D deficiency in an iranian population: season-specific vitamin D status.

BACKGROUND: Genome-wide association studies in Western countries indicate a considerable impact of variations in vitamin D binding protein (GC) genes on serum concentrations of 25-hydroxyvitamin D (25(OH)D). We aimed to investigate an association between rs2282679 polymorphism in GC and vitamin D deficiency. METHODS: A cross-sectional study conducted in the framework of the Tehran Cardio-Metabolic Genetic Study (TCGS) cohort. A total of 1568 participants aged > 18 years were randomly selected, and their 25(OH) D concentration was measured. Vitamin D deficiency was assessed concerning rs228267

Pre-diagnostic DNA methylation in blood leucocytes in cutaneous melanoma; a nested case-control study within the Norwegian Women and Cancer cohort.

The prognosis of cutaneous melanoma depends on early detection, and good biomarkers for melanoma risk may provide a valuable tool to detect melanoma development at a pre-clinical stage. By studying the epigenetic profile in pre-diagnostic blood samples of melanoma cases and cancer free controls, we aimed to identify DNA methylation sites conferring melanoma risk. DNA methylation was measured at 775,528 CpG sites using the Illumina EPIC array in whole blood in incident melanoma cases (n = 183) and matched cancer-free controls (n = 183) in the Norwegian Women and Cancer cohort. Phenotypic inform

Associations of sleep and circadian phenotypes with COVID-19 susceptibility and hospitalization: an observational cohort study based on the UK Biobank and a two-sample Mendelian randomization study.

STUDY OBJECTIVES: Sleep and circadian phenotypes are associated with several diseases. The present study aimed to investigate whether sleep and circadian phenotypes were causally linked with coronavirus disease 2019 (COVID-19)-related outcomes. METHODS: Habitual sleep duration, insomnia, excessive daytime sleepiness, daytime napping, and chronotype were selected as exposures. Key outcomes included positivity and hospitalization for COVID-19. In the observation cohort study, multivariable risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated. Two-sample Mendelian randomiza

Genome-wide copy number variations as molecular diagnostic tool for cutaneous intermediate melanocytic lesions: a systematic review and individual patient data meta-analysis.

Cutaneous intermediate melanocytic neoplasms with ambiguous histopathological features are diagnostically challenging. Ancillary cytogenetic techniques to detect genome-wide copy number variations (CNVs) might provide a valuable tool to allow accurate classification as benign (nevus) or malignant (melanoma). However, the CNV cut-off value to distinguish intermediate lesions from melanoma is not well defined. We performed a systematic review and individual patient data meta-analysis to evaluate the use of CNVs to classify intermediate melanocytic lesions. A total of 31 studies and 431 individua

Genome-wide association analysis of 95 549 individuals identifies novel loci and genes influencing optic disc morphology.

Optic nerve head morphology is affected by several retinal diseases. We measured the vertical optic disc diameter (DD) of the UK Biobank (UKBB) cohort (N = 67 040) and performed the largest genome-wide association study (GWAS) of DD to date. We identified 81 loci (66 novel) for vertical DD. We then replicated the novel loci in International Glaucoma Genetic Consortium (IGGC, N = 22 504) and European Prospective Investigation into Cancer-Norfolk (N = 6005); in general the concordance in effect sizes was very high (correlation in effect size estimates 0.90): 44 of the 66 novel loci were signific…

Genome-wide association meta-analysis of fish and EPA+DHA consumption in 17 US and European cohorts.

BACKGROUND: Regular fish and omega-3 consumption may have several health benefits and are recommended by major dietary guidelines. Yet, their intakes remain remarkably variable both within and across populations, which could partly owe to genetic influences. OBJECTIVE: To identify common genetic variants that influence fish and dietary eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) consumption. DESIGN: We conducted genome-wide association (GWA) meta-analysis of fish (n = 86,467) and EPA+DHA (n = 62,265) consumption in 17 cohorts of European descent from the CHARGE (Cohorts for Hea

Pathway analyses implicate glial cells in schizophrenia.

BACKGROUND: The quest to understand the neurobiology of schizophrenia and bipolar disorder is ongoing with multiple lines of evidence indicating abnormalities of glia, mitochondria, and glutamate in both disorders. Despite high heritability estimates of 81% for schizophrenia and 75% for bipolar disorder, compelling links between findings from neurobiological studies, and findings from large-scale genetic analyses, are only beginning to emerge. METHOD: Ten publically available gene sets (pathways) related to glia, mitochondria, and glutamate were tested for association to schizophrenia and bip

Increased risk of stroke in oral contraceptive users carried replicated genetic variants: a population-based case-control study in China.

Combined oral contraceptives (COC) use is a unique risk factor for stroke in women, and may modify the associations between genetic polymorphisms and stroke. To investigate whether the genetic variants identified in a recent genome-wide association study (GWAS) could be replicated in Chinese women, as well as, whether related risk was different in COC users, 451 stroke cases and 831 age- and region-matched controls were recruited from our cohort. Genotyping of 3 SNPs (rs700651, rs10958409, and rs1333040) was performed by the polymerase chain reaction assay with TaqMan probes. The history of co…

Wnt signaling and Dupuytren's disease.

BACKGROUND: Dupuytren's disease is a benign fibromatosis of the hands and fingers that leads to flexion contractures. We hypothesized that multiple genetic and environmental factors influence susceptibility to this disease and sought to identify susceptibility genes to better understand its pathogenesis. METHODS: We conducted a genomewide association study of 960 Dutch persons with Dupuytren's disease and 3117 controls (the discovery set) to test for association between the disease and genetic markers. We tested the 35 single-nucleotide polymorphisms (SNPs) most strongly associated with Dupuy

Epigenome-Wide Association Study Reveals Differential Methylation Sites and Association of Gene Expression Regulation with Ischemic Moyamoya Disease in Adults.

BACKGROUND: The association of DNA methylation with the pathogenesis of adult ischemic moyamoya disease (MMD) is unknown. Here, we investigated the genome-wide DNA methylation profiles in patients with MMD and identified the genes related to the pathogenesis of MMD. METHODS: Whole blood samples were collected from 20 individuals, including 10 patients with ischemic moyamoya disease without any underlying disease and 10 healthy individuals. Genome-wide DNA methylation analysis was performed using Illumina 850K microarrays. Transcriptional correlation was verified using quantitative reverse tra

Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects.

Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639). Statistics of association from each cohort were combined meta-analytically us

Gene-Smoking Interaction Analysis for the Identification of Novel Asthma-Associated Genetic Factors.

Asthma is a complex heterogeneous disease caused by gene-environment interactions. Although numerous genome-wide association studies have been conducted, these interactions have not been systemically investigated. We sought to identify genetic factors associated with the asthma phenotype in 66,857 subjects from the Health Examination Study, Cardiovascular Disease Association Study, and Korea Association Resource Study cohorts. We investigated asthma-associated gene-environment (smoking status) interactions at the level of single nucleotide polymorphisms, genes, and gene sets. We identified two

Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression.

Kashin-Beck disease (KBD) is a serious osteoarthropathia, mainly characterized by excessive chondrocyte necrosis and apoptosis. The molecula … KBD using Affymetrix Human SNP Array 6.0 in 1717 Chinese Han subjects. PLINK software was used for genome-wide association study (GWAS) of KBD. A modified gene set enrichment algorithm was applied for pathway association analysis based on GWAS results. The KBD-associated pathways were compared with abnormally expressed pathways in KBD articular cartilage, identified by microa …

Genomic study in Mexicans identifies a new locus for triglycerides and refines European lipid loci.

BACKGROUND: The Mexican population and others with Amerindian heritage exhibit a substantial predisposition to dyslipidemias and coronary heart disease. Yet, these populations remain underinvestigated by genomic studies, and to date, no genome-wide association (GWA) studies have been reported for lipids in these rapidly expanding populations. METHODS AND FINDINGS: We performed a two-stage GWA study for hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) in Mexicans (n=4361), and identified a novel Mexican-specific genome-wide significant locus for serum triglycerides (TG

Six new coeliac disease loci replicated in an Italian population confirm association with coeliac disease.

BACKGROUND AND AIMS: The first genome wide association study on coeliac disease (CD) and its follow-up have identified eight new loci that contribute significantly towards CD risk. Seven of these loci contain genes controlling adaptive immune responses, including IL2/IL21 (4q27), RGS1 (1q31), IL18RAP (2q11-2q12), CCR3 (3p21), IL12A (3q25-3q26), TAGAP (6q25) and SH2B3 (12q24). METHODS: We selected the nine most associated single nucleotide polymorphisms to tag the eight new loci in an Italian cohort comprising 538 CD patients and 593 healthy controls. RESULTS: Common variation in IL2/IL21, RG