Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide meta-analysis identifies novel loci associated with parathyroid hormone level.

ABSTRACT: BACKGROUND:Parathyroid hormone (PTH) is one of the principal regulators of calcium homeostasis. Although serum PTH level is mostly accounted by genetic factors, genetic background underlying PTH level is insufficiently known. Therefore, the aim of this study was to identify novel genetic variants associated with PTH levels. METHODS:We performed GWAS meta-analysis within two genetically isolated Croatian populations followed by replication analysis in a Croatian mainland population and we also combined results across all three analyzed populations. The analyses included 2596 individuals. A total of 7,411,206 variants, imputed using the 1000 Genomes reference panel, were analysed for the association. In addition, a sex-specific GWAS meta-analyses were performed. RESULTS:Polymorphisms with the lowest P-values were located on chromosome 4 approximately 84 kb of the 5' of RASGEF1B gene. The most significant SNP was rs11099476 (P?=?1.15?×?10-8). Sex-specific analysis identified genome-wide significant association of the variant rs77178854, located within DPP10 gene in females only (P?=?2.21?×?10-?9). There were no genome-wide significant findings in the meta-analysis of males. CONCLUSIONS:We identified two biologically plausible novel loci associated with PTH levels, providing us with further insights into the genetics of this complex trait.

SUBMITTER: Matana A

PROVIDER: S-EPMC6016867 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Genome-wide meta-analysis identifies 3 novel loci associated with stroke.

Project description:We conducted a European-only and transancestral genome-wide association meta-analysis in 72,147 stroke patients and 823,869 controls using data from UK Biobank (UKB) and the MEGASTROKE consortium. We identified an exonic polymorphism in NOS3 (rs1799983, p.Glu298Asp; p = 2.2E-8, odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1.04-1.07) and variants in an intron of COL4A1 (rs9521634; p = 3.8E-8, OR = 1.04, 95% CI = 1.03-1.06) and near DYRK1A (rs720470; p = 6.1E-9, OR = 1.05, 95% CI = 1.03-1.07) at genome-wide significance for stroke. Effect sizes of known stroke loci were highly correlated between UKB and MEGASTROKE. Using Mendelian randomization, we further show that genetic variation in the nitric oxide synthase-nitric oxide pathway in part affects stroke risk via variation in blood pressure. Ann Neurol 2018;84:934-939.

| S-EPMC6644297 | biostudies-literature

Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci.

Project description:OBJECTIVE:Taxane containing chemotherapy extends survival for breast cancer patients. However, taxane-induced peripheral neuropathy (TIPN) cannot be predicted, prevented or effectively treated. Using genome-wide analyses, we sought to identify common risk variants for TIPN. PATIENTS AND METHODS:Women with high-risk breast cancer enrolled in SWOG 0221 were genotyped using the Illumina 1M chip. Genome-wide analyses were performed in relation to ?grade 3 Common Terminology Criteria for Adverse Events (CTCAE) neuropathy in European and African Americans. Data were meta-analyzed with GW associations of CTCAE ?grade 3 versus <grade 3 in CALGB 40101 assuming a fixed effects model. RESULTS:The percentage of ?grade 3 TIPN in 1269 European Americans and 139 African Americans in S0221, was 11.6 and 22.3%, respectively. CALGB 40101 ?grade 3 TOPN was 7.2%. The most significant association with ?grade 3 TIPN was the G allele of rs1858826 in GNGT1 (Pmeta=1.1×10), which showed a decrease in risk of ?grade 3 TIPN (odds ratio=0.29, 95% confidence interval: 0.18-0.46). CONCLUSION:The genetic variants associated with ?grade 3 TIPN are hypothesized to have biochemical functions and reside in and near genes involved in diabetes and diabetic neuropathy. This finding is consistent with results from CALGB 40101 pathway analyses. Larger homogeneous trials with similar dosing and criteria for defining neuropathy are needed to properly assess the relationship of genomics with the neuropathy spectrum.

| S-EPMC5824720 | biostudies-literature

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Project description:Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30?062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

| S-EPMC4388784 | biostudies-literature

Genome-wide association meta-analysis identifies two novel loci associated with dental caries.

Project description:BackgroundTooth loss significantly impacts oral function and overall health deterioration. Dental caries and periodontal disease are major contributors to tooth loss, emphasizing the critical need to prevent these conditions. Genetic studies have played a crucial role in deepening our understanding of the underlying mechanisms of these diseases. While large-scale genome-wide association studies (GWAS) on dental caries and periodontal disease have been conducted extensively, research focusing on Asian populations remains limited. Given substantial genetic and lifestyle variations across ethnicities, conducting studies across diverse populations is imperative. This study aimed to uncover new insights into the genetic mechanisms of these diseases, contributing to broader knowledge and potential targeted interventions.MethodsWe conducted a GWAS using genome data from 45,525 Japanese individuals, assessing their self-reported history of dental caries and periodontal disease. Additionally, we performed a meta-analysis by integrating our results with those from a previous large-scale GWAS predominantly involving European populations.ResultsWhile no new loci associated with periodontal disease were identified, we discovered two novel loci associated with dental caries. The lead variants of these loci were intron variant rs10974056 in GLIS3 and intron variant rs4801882 in SIGLEC5.ConclusionOur study findings are anticipated to advance understanding of the underlying mechanisms of dental caries and periodontal disease. Thes insights may inform better management strategies for patients affected by these conditions.

| S-EPMC11348739 | biostudies-literature

Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.

Project description:To perform a 1-stage meta-analysis of genome-wide association studies (GWAS) of multiple sclerosis (MS) susceptibility and to explore functional consequences of new susceptibility loci.We synthesized 7 MS GWAS. Each data set was imputed using HapMap phase II, and a per single nucleotide polymorphism (SNP) meta-analysis was performed across the 7 data sets. We explored RNA expression data using a quantitative trait analysis in peripheral blood mononuclear cells (PBMCs) of 228 subjects with demyelinating disease.We meta-analyzed 2,529,394 unique SNPs in 5,545 cases and 12,153 controls. We identified 3 novel susceptibility alleles: rs170934(T) at 3p24.1 (odds ratio [OR], 1.17; p = 1.6 × 10(-8)) near EOMES, rs2150702(G) in the second intron of MLANA on chromosome 9p24.1 (OR, 1.16; p = 3.3 × 10(-8)), and rs6718520(A) in an intergenic region on chromosome 2p21, with THADA as the nearest flanking gene (OR, 1.17; p = 3.4 × 10(-8)). The 3 new loci do not have a strong cis effect on RNA expression in PBMCs. Ten other susceptibility loci had a suggestive p < 1 × 10(-6) , some of these loci have evidence of association in other inflammatory diseases (ie, IL12B, TAGAP, PLEK, and ZMIZ1).We have performed a meta-analysis of GWAS in MS that more than doubles the size of previous gene discovery efforts and highlights 3 novel MS susceptibility loci. These and additional loci with suggestive evidence of association are excellent candidates for further investigations to refine and validate their role in the genetic architecture of MS.

| S-EPMC3247076 | biostudies-literature

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Mullerian hormone levels in women.

Project description:Anti-Müllerian hormone (AMH) is expressed by antral stage ovarian follicles in women. Consequently, circulating AMH levels are detectable until menopause. Variation in age-specific AMH levels has been associated with breast cancer and polycystic ovary syndrome (PCOS), amongst other diseases. Identification of genetic variants underlying variation in AMH levels could provide clues about the physiological mechanisms that explain these AMH-disease associations. To date, only one variant in MCM8 has been identified to be associated with circulating AMH levels in women. We aimed to identify additional variants for AMH through a GWAS meta-analysis including data from 7049 premenopausal women of European ancestry, which more than doubles the sample size of the largest previous GWAS. We identified four loci associated with AMH levels at p < 5×10 -8 : the previously reported MCM8 locus and three novel signals in or near AMH, TEX41 , and CDCA7 . The strongest signal was a missense variant in the AMH gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among SNPs for AMH levels and for age at menopause (r g = 0.82, FDR=0.003). Exploratory Mendelian randomization analyses did not support a causal effect of AMH on breast cancer or PCOS risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored. In conclusion, we identified a variant in the AMH gene and three other loci that may affect circulating AMH levels in women.

| S-EPMC7654897 | biostudies-literature

Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Mullerian hormone levels in women.

Project description: Not available

| S-EPMC9071229 | biostudies-literature

Genome-Wide Meta-Analysis Identifies Two Novel Risk Loci for Epilepsy.

Project description:Epilepsy (affects about 70 million people worldwide) is one of the most prevalent brain disorders and imposes a huge economic burden on society. Epilepsy has a strong genetic component. In this study, we perform the largest genome-wide meta-analysis of epilepsy (N = 8,00,869 subjects) by integrating four large-scale genome-wide association studies (GWASs) of epilepsy. We identified three genome-wide significant (GWS) (p < 5 × 10-8) risk loci for epilepsy. The risk loci on 7q21.11 [lead single nucleotide polymorphism (SNP) rs11978015, p = 9.26 × 10-9] and 8p23.1 (lead SNP rs28634186, p = 4.39 × 10-8) are newly identified in the present study. Of note, rs11978015 resides in upstream of GRM3, which encodes glutamate metabotropic receptor 3. GRM3 has pivotal roles in neurotransmission and is involved in most aspects of normal brain function. In addition, we also identified three genes (TTC21B, RP11-375N15.2, and TNKS) whose cis-regulated expression level are associated with epilepsy, indicating that risk variants may confer epilepsy risk through regulating the expression of these genes. Our study not only provides new insights into genetic architecture of epilepsy but also prioritizes potential molecular targets (including GRM3 and TTC21B) for development of new drugs and therapeutics for epilepsy.

| S-EPMC8397525 | biostudies-literature

Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology.

Project description:Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma.

| S-EPMC4480365 | biostudies-literature

Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris.

Project description:Acne vulgaris is a common chronic skin disorder presenting with comedones, cystic structures forming within the distal hair follicle, and in most cases additionally with inflammatory skin lesions on the face and upper torso. We performed a genome-wide association study and meta-analysis of data from 34,422 individuals with acne and 364,991 controls from three independent European-ancestry cohorts. We replicated 19 previously implicated genome-wide significant risk loci and identified four novel loci [11q12.2 (FADS2), 12q21.1 (LGR5), 17q25.3 (FASN), and 22q12.1 (ZNRF3-KREMEN1)], bringing the total number of reported acne risk loci to 50. Our meta-analysis results explain 9.4% of the phenotypic variance of acne. A polygenic model of acne risk variants showed that individuals in the top 5% of the risk percentiles had a 1.62-fold (95% CI 1.47-1.78) increased acne risk relative to individuals with average risk (20-80% on the polygenic risk score distribution). Our findings highlight the Wnt and MAPK pathways as key factors in the genetic predisposition to acne vulgaris, together with the effects of genetic variation on the structure and maintenance of the hair follicle and pilosebaceous unit. Two novel loci, 11q12.2 and 17q25.3, contain genes encoding key enzymes involved in lipid biosynthesis pathways.

| S-EPMC11368920 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data