scholarly journals Trans-Ethnic Mapping of BANK1 Identifies Two Independent SLE-Risk Linkage Groups Enriched for Co-Transcriptional Splicing Marks

2018 ◽  
Vol 19 (8) ◽  
pp. 2331 ◽  
Author(s):  
Manuel Martínez-Bueno ◽  
Nina Oparina ◽  
Mikhail Dozmorov ◽  
Miranda Marion ◽  
Mary Comeau ◽  
...  
Keyword(s):  
B Cell ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Eqtl Analysis ◽  
Minimal Set ◽  
Genome Wide ◽  
Trait Locus ◽  
Independent Effects ◽  
Ethnic Mapping ◽  
Splice Junctions

BANK1 is a susceptibility gene for several systemic autoimmune diseases in several populations. Using the genome-wide association study (GWAS) data from Europeans (EUR) and African Americans (AA), we performed an extensive fine mapping of ankyrin repeats 1 (BANK1). To increase the SNP density, we used imputation followed by univariate and conditional analysis, combined with a haplotypic and expression quantitative trait locus (eQTL) analysis. The data from Europeans showed that the associated region was restricted to a minimal and dependent set of SNPs covering introns two and three, and exon two. In AA, the signal found in the Europeans was split into two independent effects. All of the major risk associated SNPs were eQTLs, and the risks were associated with an increased BANK1 gene expression. Functional annotation analysis revealed the enrichment of repressive B cell epigenomic marks (EZH2 and H3K27me3) and a strong enrichment of splice junctions. Furthermore, one eQTL located in intron two, rs13106926, was found within the binding site for RUNX3, a transcriptional activator. These results connect the local genome topography, chromatin structure, and the regulatory landscape of BANK1 with co-transcriptional splicing of exon two. Our data defines a minimal set of risk associated eQTLs predicted to be involved in the expression of BANK1 modulated through epigenetic regulation and splicing. These findings allow us to suggest that the increased expression of BANK1 will have an impact on B-cell mediated disease pathways.

scholarly journals A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 751
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Integrated Analysis ◽  
Eqtl Analysis ◽  
Strong Linkage Disequilibrium ◽  
Genome Wide ◽  
A Genome

Hypertension is one of the major risk factors for chronic kidney disease (CKD), and the coexistence of hypertension and CKD increases morbidity and mortality. Although many genetic factors have been identified separately for hypertension and kidney disease, studies specifically focused on hypertensive kidney disease (HKD) have been rare. Therefore, this study aimed to identify loci or genes associated with HKD. A genome-wide association study (GWAS) was conducted using two Korean cohorts, the Health Examinee (HEXA) and Korean Association REsource (KARE). Consequently, 19 single nucleotide polymorphisms (SNPs) were found to be significantly associated with HKD in the discovery and replication phases (p < 5 × 10−8, p < 0.05, respectively). We further analyzed HKD-related traits such as the estimated glomerular filtration rate (eGFR), creatinine, blood urea nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the 14q21.2 locus, which showed a strong linkage disequilibrium (LD). Expression quantitative trait loci (eQTL) analysis was also performed to determine whether HKD-related SNPs affect gene expression changes in glomerular and arterial tissues. The results suggested that the FANCM gene may affect the development of HKD through an integrated analysis of eQTL and GWAS and was the most significantly associated candidate gene. Taken together, this study indicated that the FANCM gene is involved in the pathogenesis of HKD. Additionally, our results will be useful in prioritizing other genes for further experiments.

scholarly journals Genome-Wide Association Study Identifies ALDH7A1 as a Novel Susceptibility Gene for Osteoporosis

PLoS Genetics ◽  
2010 ◽  
Vol 6 (1) ◽  
pp. e1000806 ◽  
Author(s):  
Yan Guo ◽  
Li-Jun Tan ◽  
Shu-Feng Lei ◽  
Tie-Lin Yang ◽  
Xiang-Ding Chen ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Genome Wide Association ◽  
Genome Wide

scholarly journals DIRC3-IGFBP5 is a shared genetic risk locus and therapeutic target for carpal tunnel syndrome and trigger finger

2021 ◽  
Author(s):  
Benjamin Patel ◽  
Sam O. Kleeman ◽  
Drew Neavin ◽  
Joseph Powell ◽  
Georgios Baskozos ◽  
...  
Keyword(s):  
Carpal Tunnel Syndrome ◽  
Carpal Tunnel ◽  
Genome Wide Association Study ◽  
Trigger Finger ◽  
Eqtl Analysis ◽  
Genome Wide ◽  
Healthy Donors ◽  
A Genome ◽  
Tunnel Syndrome ◽  
Shared Genetic

AbstractTrigger finger (TF) and carpal tunnel syndrome (CTS) are two common non-traumatic hand disorders that frequently co-occur. By identifying TF and CTS cases in UK Biobank (UKB), we confirmed a highly significant phenotypic association between the diseases. To investigate the genetic basis for this association we performed a genome-wide association study (GWAS) including 2,908 TF cases and 436,579 European controls in UKB, identifying five independent loci. Colocalization with CTS summary statistics identified a co-localized locus at DIRC3 (lncRNA), which was replicated in FinnGen and fine-mapped to rs62175241. Single-cell and bulk eQTL analysis in fibroblasts from healthy donors (n=79) and tenosynovium samples from CTS patients (n=77) showed that the disease-protective rs62175241 allele was associated with increased DIRC3 and IGFBP5 expression. IGFBP5 is a secreted antagonist of IGF-1 signaling, and elevated IGF-1 levels were associated with CTS and TF in UKB, thereby implicating IGF-1 as a driver of both diseases.

scholarly journals Genome-wide association study of antipsychotic-induced sinus bradycardia in Chinese schizophrenia patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249997
Author(s):  
Saizheng Weng ◽  
Bo Wang ◽  
Mo Li ◽  
Shan Chao ◽  
Ruiqian Lin ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Sinus Bradycardia ◽  
Susceptibility Gene ◽  
Han Chinese ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

Second-generation antipsychotics (SGAs) play a critical role in current treatment of schizophrenia (SCZ). It has been observed that sinus bradycardia, rare but in certain situations life threatening adverse drug reaction, can be induced by SGAs across different schizophrenia populations. However, the roles of genetic factors in this phenomenon have not been studied yet. In the present study, a genome-wide association study of single nucleotide polymorphisms (SNPs) was performed on Chinese Han SCZ patients to identify susceptibility loci that were associated with sinus bradycardia induced by SGAs. This study applied microarray to obtain genotype profiles of 88 Han Chinese SCZ patients. Our results found that there were no SNPs had genome-wide significant association with sinus bradycardia induced by SGAs. The top GWAS hit located in gene KIAA0247, which mainly regulated by the tumor suppressor P53 and thus plays a role in carcinogenesis based on resent research and it should not be a susceptibility locus to sinus bradycardia induced by SGAs. Using gene-set functional analysis, we tested that if top 500 SNPs mapped genes were relevant to sinus bradycardia. The result of gene prioritization analysis showed CTNNA3 was strongly correlated with sinus bradycardia, hinting it was a susceptibility gene of this ADR. Our study provides a preliminary study of genetic variants associated with sinus bradycardia induced by SGAs in Han Chinese SCZ patients. The discovery of a possible susceptibility gene shed light on further study of this adverse drug reaction in Han Chinese SCZ patients.

scholarly journals A compendium of uniformly processed human gene expression and splicing quantitative trait loci

2021 ◽  
Vol 53 (9) ◽  
pp. 1290-1299
Author(s):  
Nurlan Kerimov ◽  
James D. Hayhurst ◽  
Kateryna Peikova ◽  
Jonathan R. Manning ◽  
Peter Walter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Target Genes ◽  
Genome Wide Association Study ◽  
Cell Types ◽  
Summary Statistics ◽  
Genome Wide ◽  
Cell Type Specific ◽  
Trait Locus ◽  
Complex Human Traits

AbstractMany gene expression quantitative trait locus (eQTL) studies have published their summary statistics, which can be used to gain insight into complex human traits by downstream analyses, such as fine mapping and co-localization. However, technical differences between these datasets are a barrier to their widespread use. Consequently, target genes for most genome-wide association study (GWAS) signals have still not been identified. In the present study, we present the eQTL Catalogue (https://www.ebi.ac.uk/eqtl), a resource of quality-controlled, uniformly re-computed gene expression and splicing QTLs from 21 studies. We find that, for matching cell types and tissues, the eQTL effect sizes are highly reproducible between studies. Although most QTLs were shared between most bulk tissues, we identified a greater diversity of cell-type-specific QTLs from purified cell types, a subset of which also manifested as new disease co-localizations. Our summary statistics are freely available to enable the systematic interpretation of human GWAS associations across many cell types and tissues.

Genome-wide association study identifies TNFSF13 as a susceptibility gene for IgA in a South Chinese population in smokers

2012 ◽  
Vol 64 (10) ◽  
pp. 747-753 ◽  
Author(s):  
Chen Yang ◽  
Wang Jie ◽  
Yang Yanlong ◽  
Guo Xuefeng ◽  
Tan Aihua ◽  
...  
Keyword(s):  
Association Study ◽  
Chinese Population ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Genome Wide Association ◽  
Genome Wide

Replication study of 10 genes showing evidence for association with multiple sclerosis: validation of TMEM39A, IL12B and CLBL genes

2011 ◽  
Vol 18 (7) ◽  
pp. 959-965 ◽  
Author(s):  
Jezabel Varadé ◽  
Manuel Comabella ◽  
Miguel A Ortiz ◽  
Rafael Arroyo ◽  
Oscar Fernández ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Diseases ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Pooled Analysis ◽  
Replication Study ◽  
Genome Wide Association ◽  
Genome Wide

Background and objectives: Ten genes previously showing different evidence of association with multiple sclerosis have been selected to validate. Methods: Eleven polymorphisms were genotyped with the iPLEX™ Sequenom in a well-powered collection of Spanish origin including 2863 multiple sclerosis cases and 2930 controls. Results: Replication extended to the following polymorphisms: PKN2 (rs305217), GTF2B (rs7538427), EPHA4 (rs1517440), YTHDF3 (rs12115114), ANKFN1 (rs17758761) and PTPRM (rs4798571), which did not reach the threshold of significance in a follow-up of the first genome-wide association study (GWAS) conducted in multiple sclerosis; TMEM39A (rs1132200), which appeared as a newly identified susceptibility gene in the same study; a gene previously reaching GWAS significance in Italy, CBLB (rs9657904); IL12B (rs6887695, rs10045431), a susceptibility gene shared by diverse autoimmune diseases and, finally, another gene showing inconclusive association with multiple sclerosis, CNR1 (rs1049353). Conclusions: Pooled analysis corroborated the effect on MS predisposition of three genes: TMEM39A [rs1132200: pM-H=0.001; ORM-H (95% CI)= 0.84 (0.75–0.93)], IL12B [rs6887695: pM-H=0.03; ORM-H (95% CI)= 1.09 (1.01–1.17)] and CBLB [rs9657904: pM-H=0.01; ORM-H (95% CI)= 0.89 (0.81–0.97)].

scholarly journals Gene duplication confers enhanced expression of 27-kDa γ-zein for endosperm modification in quality protein maize

2016 ◽  
Vol 113 (18) ◽  
pp. 4964-4969 ◽  
Author(s):  
Hongjun Liu ◽  
Junpeng Shi ◽  
Chuanlong Sun ◽  
Hao Gong ◽  
Xingming Fan ◽  
...  
Keyword(s):  
Linkage Mapping ◽  
Genome Wide Association Study ◽  
Genetic Selection ◽  
Quality Protein Maize ◽  
Genome Wide ◽  
Mapping Analysis ◽  
Enhanced Expression ◽  
Selection For ◽  
Trait Locus ◽  
Maize Domestication

The maize opaque2 (o2) mutant has a high nutritional value but it develops a chalky endosperm that limits its practical use. Genetic selection for o2 modifiers can convert the normally chalky endosperm of the mutant into a hard, vitreous phenotype, yielding what is known as quality protein maize (QPM). Previous studies have shown that enhanced expression of 27-kDa γ-zein in QPM is essential for endosperm modification. Taking advantage of genome-wide association study analysis of a natural population, linkage mapping analysis of a recombinant inbred line population, and map-based cloning, we identified a quantitative trait locus (qγ27) affecting expression of 27-kDa γ-zein. qγ27 was mapped to the same region as the major o2 modifier (o2 modifier1) on chromosome 7 near the 27-kDa γ-zein locus. qγ27 resulted from a 15.26-kb duplication at the 27-kDa γ-zein locus, which increases the level of gene expression. This duplication occurred before maize domestication; however, the gene structure of qγ27 appears to be unstable and the DNA rearrangement frequently occurs at this locus. Because enhanced expression of 27-kDa γ-zein is critical for endosperm modification in QPM, qγ27 is expected to be under artificial selection. This discovery provides a useful molecular marker that can be used to accelerate QPM breeding.

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