Browse
Submit Data
Databases
API
Help

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Germline variants at SOHLH2 influence multiple myeloma risk.

ABSTRACT: Multiple myeloma (MM) is caused by the uncontrolled, clonal expansion of plasma cells. While there is epidemiological evidence for inherited susceptibility, the molecular basis remains incompletely understood. We report a genome-wide association study totalling 5,320 cases and 422,289 controls from four Nordic populations, and find a novel MM risk variant at SOHLH2 at 13q13.3 (risk allele frequency = 3.5%; odds ratio = 1.38; P = 2.2 × 10^-14). This gene encodes a transcription factor involved in gametogenesis that is normally only weakly expressed in plasma cells. The association is represented by 14 variants in linkage disequilibrium. Among these, rs75712673 maps to a genomic region with open chromatin in plasma cells, and upregulates SOHLH2 in this cell type. Moreover, rs75712673 influences transcriptional activity in luciferase assays, and shows a chromatin looping interaction with the SOHLH2 promoter. Our work provides novel insight into MM susceptibility.

SUBMITTER: Duran-Lozano L

PROVIDER: S-EPMC8055668 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Germline Risk Contribution to Genomic Instability in Multiple Myeloma.

Project description: Not available

| S-EPMC6518313 | biostudies-literature

BSG and MCT1 Genetic Variants Influence Survival in Multiple Myeloma Patients.

Project description: Not available

| S-EPMC5977166 | biostudies-literature

Cereblon and IRF4 Variants Affect Risk and Response to Treatment in Multiple Myeloma.

Project description: Not available

| S-EPMC5334380 | biostudies-literature

ADME gene variants in multiple myeloma susceptibility

Project description:The metabolism of xenobiotics is regulated by phase I and II enzymes, and by transporters encoded by the absorption, distribution, metabolism, and excretion (ADME) genes. It is known that the activity of these proteins is influenced by the presence of polymorphic variants in the corresponding gene that can account for the inter-individual variability in both xenobiotic response/toxicity and disease predisposition. Exposure to pesticides and toxic substances, many of which are substrates of ADME-associated proteins, has been demonstrated to increase the risk of Multiple Myeloma (MM). To investigate the inter-individual variability of ADME genes as a risk factor for MM risk, we compared DMET Plus genotyping data from 65 MM patients with 59 CEU Hapmap controls (GPL17860).

2021-11-03 | GSE187009 | GEO

Identification of Germline Genetic Variants that Increase Prostate Cancer Risk and Influence Development of Aggressive Disease.

Project description: Not available

| S-EPMC7917798 | biostudies-literature

Identification of rare germline variants in familial multiple myeloma

Project description:The risk of developing multiple myeloma (MM) in first-degree relatives of affected individuals is 2 to 4 fold higher than in the general population, implying the existence of inherited susceptibility. While over 20 common, low-penetrance variants have been associated with MM risk, less is known about rare, high-penetrance germline predisposition. We aimed to identify and characterize high/moderated penetrance germline variants in MM families using whole genome sequencing. For that purpose we identified families with at least two individuals diagnosed with MM or its precursors MGUS and smoldering MM. Also, patients with solitary plasmacytoma and AL amyloidosis were enrolled. We also recruited unaffected family members, and they were screened to exclude undetected MM or its precursor stages. After whole genome sequencing of blood DNA and filtering for rare variants (minor allele frequency <0.1%) and family segregation, variants are prioritized by a range of published in silico tools and literature search. The most promising variants are subjected to experimental validation to evaluate their functional relevance. Our data will provide guidance to worldwide efforts to unravel germline predisposition in MM and validation of the proposed variants and genes.

| EGAS00001004734 | EGA

Revealing the impact of structural variants in multiple myeloma.

Project description: Not available

| S-EPMC7774871 | biostudies-literature

Germline Genetic Risk Variants for Progressive Multifocal Leukoencephalopathy.

Project description: Not available

| S-EPMC7094807 | biostudies-literature

Genetic Risk Variants for Autoimmune Diseases that Influence Gene Expression in Thymus

Project description:Genome-wide association studies (GWAS) have boosted our knowledge of genetic risk variants in autoimmune diseases (AIDs). Most of the risk variants are located within or near genes with immunological functions, and the majority is found to be non-coding, pointing towards a regulatory role. We have performed a cis expression quantitative trait locus (eQTL) screen to investigate whether single nucleotide polymorphisms (SNPs) associated with AIDs influence gene expression in thymus. Genotyping was performed using the Immunochip and 353 AID associated SNPs were tested against expression of surrounding genes (+/- 1 Mb) from human thymic tissue (N=42). We identified eight genes where the expression was associated with AID risk SNPs at a study-wide level of significance (P < 2.57x10-5). Five genes (FCRL3, RNASET2, C2orf74, SIRPG and SYS1) displayed cis eQTL signals also in other tissues, while for two loci (NPIPB8 and LOC388814), the eQTL signal appear to be thymus-specific. Since many AID risk variants from GWAS have been subsequently fine-mapped in recent Immunochip projects, we explored the overlap between these novel AID risk variants and the thymic eQTL regions. Moreover, we examined the functional annotation of the seven expression altering SNPs (eSNPs). Our study reveals autoimmune risk variants that act as eQTLs in thymus. We have highlighted functional variants within these genetic regions that potentially can represent causal autoimmune risk variants. Total RNA from 42 human thymic samples were obtained from children undergoing cardiac surgery.

2016-01-21 | E-GEOD-77052 | biostudies-arrayexpress

Germline Lysine-Specific Demethylase 1 (LSD1/KDM1A) Mutations Confer Susceptibility to Multiple Myeloma.

Project description: Not available

| S-EPMC5955848 | biostudies-literature