Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q.

ABSTRACT: Plasma lipoprotein(a) (Lp[a]) level is an independent risk factor of cardiovascular disease that is under strong genetic control. We conducted a genome-wide association study of plasma Lp(a) in 386 members of a founder population that adheres to a communal lifestyle, proscribes cigarette smoking, and prepares and eats meals communally. We identified associations with 77 single nucleotide polymorphisms (SNPs) spanning 12.5 Mb on chromosome 6q26-q27 that met criteria for genome-wide significance (P

SUBMITTER: Ober C

PROVIDER: S-EPMC2666166 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Genome-wide association study of plasma lipoprotein(a) levels identifies multiple genes on chromosome 6q.

Ober Carole C Nord Alex S AS Thompson Emma E EE Pan Lin L Tan Zheng Z Cusanovich Darren D Sun Ying Y Nicolae Raluca R Edelstein Celina C Schneider Daniel H DH Billstrand Christine C Pfaffinger Ditta D Phillips Natasha N Anderson Rebecca L RL Philips Binu B Rajagopalan Ramakrishnan R Hatsukami Thomas S TS Rieder Mark J MJ Heagerty Patrick J PJ Nickerson Deborah A DA Abney Mark M Marcovina Santica S Jarvik Gail P GP Scanu Angelo M AM Nicolae Dan L DL

Journal of lipid research 20090105 5

Plasma lipoprotein(a) (Lp[a]) level is an independent risk factor of cardiovascular disease that is under strong genetic control. We conducted a genome-wide association study of plasma Lp(a) in 386 members of a founder population that adheres to a communal lifestyle, proscribes cigarette smoking, and prepares and eats meals communally. We identified associations with 77 single nucleotide polymorphisms (SNPs) spanning 12.5 Mb on chromosome 6q26-q27 that met criteria for genome-wide significance ( ...[more]

PMID: 19124843

Similar Datasets

Novel cleft susceptibility genes in chromosome 6q.

Project description:Cleft lip/palate is a defect of craniofacial development. In previous reports, chromosome 6q has been suggested as a candidate region for cleft lip/palate. A multipoint posterior probability of linkage analysis of multiplex families from the Philippines attributed an 88% probability of harboring a cleft-susceptibility gene to a narrower region on bands 6q14.2-14.3. We genotyped 2732 individuals from families and unrelated individuals with and without clefts to investigate the existence of possible cleft-susceptibility genes in this region. We found association of PRSS35 and SNAP91 genes with cleft lip/palate in the case-control cohort and in Caucasian families. Haplotype analyses support the individual associations with PRSS35. We found Prss35 expression in the head and palate of mouse embryos at critical stages for palatogenesis, whereas Snap91 was expressed in the adult brain. We provide further evidence of the involvement of chromosome 6q in cleft lip/palate and suggest PRSS35 as a novel candidate gene.

| S-EPMC2924960 | biostudies-literature

Genome-wide association study identifies two loci influencing plasma neurofilament light levels.

Project description:BACKGROUND:Plasma neurofilament light (NFL) is a promising biomarker for Alzheimer disease (AD), which increases in the early stage of AD and is associated with the progression of AD. We performed a genome-wide association study (GWAS) of plasma NFL in Alzheimer's Disease Neuroimaging Initiative 1 (ADNI-1) cohort to identify novel variants associated with AD. METHODS:This study included 179 cognitively healthy controls (HC), 176 patients with mild cognitive impairment (MCI), and 172 patients with AD. All subjects were restricted to non-Hispanic Caucasian derived from the ADNI cohort and met all quality control (QC) criteria. Association of plasma NFL with the genetic variants was assessed using PLINK with an additive genetic model, i.e.dose-dependent effect of the minor alleles. The influence of a genetic variant associated with plasma NFL (rs7943454) on brain structure was further assessed using PLINK with a linear regression model. RESULTS:The minor allele (T) of rs7943454 in leucine zipper protein 2 gene (LUZP2) was associated with higher plasma NFL at suggestive levels (P?=?1.39?×?10-?6) in a dose-dependent fashion. In contrast, the minor allele (G) of rs640476 near GABRB2 was associated with lower plasma NFL at suggestive levels (P?=?6.71?×?10-?6) in a dose-dependent effect in all diagnostic groups except the MCI group. Furthermore, the minor allele (T) of rs7943454 within LUZP2 increased the onset risk of AD (odds ratio?=?1.547, confidence interval 95%?=?1.018-2.351) and was associated with atrophy of right middle temporal gyrus in the whole cohort in the longitudinal study (P?=?0.0234). CONCLUSION:GWAS found the associations of two single nucleotide polymorphisms (rs7943454 and rs640476) with plasma NFL at suggestive levels. Rs7943454 in LUZP2 was associated with the onset risk of AD and atrophy of right middle temporal gyrusin the whole cohort. Using an endophenotype-based approach, we identified rs7943454 as a new AD risk locus.

| S-EPMC5946407 | biostudies-literature

Genome-wide association study identifies multiple loci influencing human serum metabolite levels.

Project description:Nuclear magnetic resonance assays allow for measurement of a wide range of metabolic phenotypes. We report here the results of a GWAS on 8,330 Finnish individuals genotyped and imputed at 7.7 million SNPs for a range of 216 serum metabolic phenotypes assessed by NMR of serum samples. We identified significant associations (P < 2.31 × 10(-10)) at 31 loci, including 11 for which there have not been previous reports of associations to a metabolic trait or disorder. Analyses of Finnish twin pairs suggested that the metabolic measures reported here show higher heritability than comparable conventional metabolic phenotypes. In accordance with our expectations, SNPs at the 31 loci associated with individual metabolites account for a greater proportion of the genetic component of trait variance (up to 40%) than is typically observed for conventional serum metabolic phenotypes. The identification of such associations may provide substantial insight into cardiometabolic disorders.

| S-EPMC3605033 | biostudies-literature

Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.

Project description:BackgroundWhile genome-wide association studies (GWAS) of multiple myeloma (MM) have identified variants at 23 regions influencing risk, the genes underlying these associations are largely unknown. To identify candidate causal genes at these regions and search for novel risk regions, we performed a multi-tissue transcriptome-wide association study (TWAS).ResultsGWAS data on 7319 MM cases and 234,385 controls was integrated with Genotype-Tissue Expression Project (GTEx) data assayed in 48 tissues (sample sizes, N = 80-491), including lymphocyte cell lines and whole blood, to predict gene expression. We identified 108 genes at 13 independent regions associated with MM risk, all of which were in 1 Mb of known MM GWAS risk variants. Of these, 94 genes, located in eight regions, had not previously been considered as a candidate gene for that locus.ConclusionsOur findings highlight the value of leveraging expression data from multiple tissues to identify candidate genes responsible for GWAS associations which provide insight into MM tumorigenesis. Among the genes identified, a number have plausible roles in MM biology, notably APOBEC3C, APOBEC3H, APOBEC3D, APOBEC3F, APOBEC3G, or have been previously implicated in other malignancies. The genes identified in this TWAS can be explored for follow-up and validation to further understand their role in MM biology.

| S-EPMC6700979 | biostudies-literature

Genome-wide association study identifies <i>MAPT</i> locus influencing human plasma tau levels.

Project description:ObjectiveTo identify genetic loci associated with plasma tau concentrations in healthy elders and individuals with Alzheimer disease.MethodsFour hundred sixty-three non-Hispanic white individuals exceeding quality control criteria were included from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) cohort. Association of plasma tau with genetic polymorphisms was performed with a linear regression model. Significant associations were validated in an independent replication cohort consisting of 431 healthy elders or individuals with mild cognitive impairment recruited from the University of California, San Francisco Memory and Aging Center.ResultsThe minor allele (A) of rs242557 in the microtubule-associated protein tau gene (MAPT) was associated with higher plasma tau levels at genome-wide significance (p = 4.85 × 10-9, empiric family-wise error corrected p = 0.0024) in a dose-dependent fashion. This association was also observed in the replication cohort (p = 1.0 × 10-5; joint analysis p = 1.2 × 10-12). Single nucleotide polymorphisms near PARK2 (rs2187213) (p = 6.15 × 10-6), IL2RA (rs7072793, rs7073236) (p = 7.89 × 10-6), and an intergenic locus on 9p21.3 (rs7047280) (p = 8.13 × 10-6) were identified as suggestive loci associated with plasma tau levels.ConclusionsMAPT H1c haplotype (rs242557) has previously been identified as a genetic risk factor for progressive supranuclear palsy and corticobasal degeneration. The current findings suggest that plasma tau concentration could be an endophenotype for identifying risk for 4-repeat tauopathies in older individuals.

| S-EPMC5317386 | biostudies-literature

Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels.

Project description:Metabolites are small products of metabolism that provide a snapshot of the wellbeing of an organism and the mechanisms that control key physiological processes involved in health and disease. Here we report the results of a genome-wide association study of 722 circulating metabolite levels in 8809 subjects of European origin, providing both breadth and depth. These analyses identified 202 unique genomic regions whose variations are associated with the circulating levels of 478 different metabolites. Replication with a subset of 208 metabolites that were available in an independent dataset for a cohort of 1768 European subjects confirmed the robust associations, including 74 novel genomic regions not associated with any metabolites in previous works. This study enhances our knowledge of genetic mechanisms controlling human metabolism. Our findings have major potential for identifying novel targets and developing new therapeutic strategies.

| S-EPMC8777659 | biostudies-literature

A meta-analysis of genome-wide association studies identifies multiple longevity genes.

Project description:Human longevity is heritable, but genome-wide association (GWA) studies have had limited success. Here, we perform two meta-analyses of GWA studies of a rigorous longevity phenotype definition including 11,262/3484 cases surviving at or beyond the age corresponding to the 90th/99th survival percentile, respectively, and 25,483 controls whose age at death or at last contact was at or below the age corresponding to the 60th survival percentile. Consistent with previous reports, rs429358 (apolipoprotein E (ApoE) ε4) is associated with lower odds of surviving to the 90th and 99th percentile age, while rs7412 (ApoE ε2) shows the opposite. Moreover, rs7676745, located near GPR78, associates with lower odds of surviving to the 90th percentile age. Gene-level association analysis reveals a role for tissue-specific expression of multiple genes in longevity. Finally, genetic correlation of the longevity GWA results with that of several disease-related phenotypes points to a shared genetic architecture between health and longevity.

| S-EPMC6694136 | biostudies-literature

Genome-wide association scan identifies variants near Matrix Metalloproteinase (MMP) genes on chromosome 11q21-22 strongly associated with serum MMP-1 levels.

Project description:Matrix metalloproteinase (MMP)-1 may play a role in cardiovascular disease susceptibility by influencing plaque rupture via its ability to degrade extracellular collagens.We performed a genome-wide association analysis of circulating MMP-1 levels using 500 K single-nucleotide polymorphisms (SNPs) to identify genes influencing variation in serum MMP-1 levels in 778 healthy Amish adults. Serum MMP-1 levels, logarithm transformed, and adjusted for age and sex, were screened for association with SNPs using mixed-model variance components to account for familial relatedness. Median MMP-1 level was 3.05 ng/mL (interquartile range: 1.82 to 5.04 ng/mL) with an estimated heritability of 81% (P<0.0001). Serum MMP-1 levels were strongly associated with a cluster of 179 SNPs extending over an 11.5-megabase region on chromosome 11q. The peak association was with rs495366 (P = 5.73 x 10(-34)), located within the region between MMP-1 and MMP-3 and having a minor allele frequency of 0.36. Two other SNPs within the 11q region, rs12289128 and rs11226373, were strongly associated with MMP-1 levels after accounting for rs495366 (P < or = 10(-7)). These 3 SNPs explained 31% of the variance in MMP-1 levels after adjusting for age and sex.This study provides strong evidence that the serum MMP-1 level is highly heritable and that SNPs near MMPs on chromosome 11q explain a significant portion of the variation in MMP-1 levels. Identification of the genetic variants that influence MMP-1 levels may provide insights into genetic mechanisms of cardiovascular disease.

| S-EPMC2801898 | biostudies-literature

Transcriptome-wide association study identifies multiple genes and pathways associated with pancreatic cancer.

Project description:AimTo identify novel candidate genes for pancreatic cancer.MethodsWe performed a transcriptome-wide association study (TWAS) analysis of pancreatic cancer (PC). GWAS summary data were driven from the published studies of PC, totally involving 558 542 SNPs in 1896 individuals with pancreatic cancer and 1939 healthy controls. FUSION software was applied to the PC GWAS summary data for tissue-related TWAS analysis, including whole blood, peripheral blood, adipose, and pancreas. The functional relevance of identified genes with PC was further validated by Oncomine, STRING, and CluePedia tool.ResultsTranscriptome-wide association study analysis identified 19 genes significantly associated with PC, such as LRP5L (P value = 5.21 × 10-5 ), SOX4 (P value = 3.2 × 10-4 ), and EGLN3 (P value = 6.2 × 10-3 ). KEGG pathway enrichment analysis detected several PC-associated pathways, such as One carbon pool by folate (P value = 1.60 × 10-16 ), Cell cycle (P value = 1.27 × 10-7 ), TGF-beta signaling pathway (P value = 4.64 × 10-6 ). Further comparing the 19 genes with previously identified overexpressed genes in PC patients found one overlapped gene SOX4.ConclusionWe identified some novel candidate genes and pathways associated with PC. Our results provide novel clues for the genetic mechanism studies of pancreatic cancer.

| S-EPMC6247024 | biostudies-literature

Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels.

Project description:Plasma soluble leptin receptor (sOB-R) levels were inversely associated with diabetes risk factors, including adiposity and insulin resistance, and highly correlated with the expression levels of leptin receptor, which is ubiquitously expressed in most tissues. We conducted a genome-wide association study of sOB-R in 1504 women of European ancestry from the Nurses' Health Study. The initial scan yielded 26 single nucleotide polymorphisms (SNPs) significantly associated with sOB-R levels (P < 5 x 10(-8)); all mapping to the leptin receptor gene (LEPR). Analysis of imputed genotypes on autosomal chromosomes revealed an additional 106 SNPs in and adjacent to this gene that reached genome-wide significance level. Of these 132 SNPs (including two non-synonymous SNPs, rs1137100 and rs1137101), rs2767485, rs1751492 and rs4655555 remained associated with sOB-R levels at the 0.05 level (P = 9.1 x 10(-9), 0.0105 and 0.0267, respectively) after adjustment for other univariately associated SNPs in a forward selection procedure. Significant associations with these SNPs were replicated in an independent sample of young males (n = 875) residing in Cyprus (P < 1 x 10(-4)). These data provide novel evidence revealing the role of polymorphisms in LEPR in modulating plasma levels of sOB-R and may further our understanding of the complex relationships among leptin, leptin receptor and diabetes-related traits.

| S-EPMC2850621 | 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