scholarly journals A transcriptome-wide association study identifies PALMD as a susceptibility gene for calcific aortic valve stenosis

2017 ◽  
Author(s):  
Sébastien Thériault ◽  
Nathalie Gaudreault ◽  
Maxime Lamontagne ◽  
David Messika-Zeitoun ◽  
Marie-Annick Clavel ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Association Study ◽  
Aortic Valve Stenosis ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Strong Association ◽  
Susceptibility Gene ◽  
Population Attributable Risk ◽  
Attributable Risk ◽  
A Genome

AbstractCalcific aortic valve stenosis (CAVS) is a common and life-threatening heart disease with no drug that can stop or delay its progression. Elucidating the genetic factors underpinning CAVS is an urgent priority to find new therapeutic targets1. Major landmarks in genetics of CAVS include the discoveries of NOTCH12 and LPA3. However, genetic variants in these genes accounted for a small number of cases and low population-attributable risk. Here we mapped a new susceptibility locus for CAVS on chromosome 1p21.2 and identified PALMD (palmdelphin) as the causal gene. PALMD was revealed using a transcriptome-wide association study (TWAS)4, which combines a genome-wide association study (GWAS) of 1,009 cases and 1,017 ethnically-matched controls with the first large-scale expression quantitative trait loci (eQTL) mapping study on human aortic valve tissues (n=233). The CAVS risk alleles and increasing disease severity were both associated with lowered mRNA expression levels of PALMD in valve tissues. The top variant explained up to 12.5% of the population-attributable risk and showed similar effect and strong association with CAVS (P=1.53 × 10−10) in UK Biobank comparing 1,391 cases and 352,195 controls. The identification of PALMD as a susceptibility gene for CAVS provides new insights about the genetic nature of this disease and opens new avenues to investigate its etiology and develop much-needed therapeutic options.

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.

Identification of CELSR1 as a susceptibility gene for ischemic stroke in Japanese individuals by a genome-wide association study

2009 ◽  
Vol 207 (1) ◽  
pp. 144-149 ◽  
Author(s):  
Yoshiji Yamada ◽  
Noriyuki Fuku ◽  
Masashi Tanaka ◽  
Yukitoshi Aoyagi ◽  
Motoji Sawabe ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals A Genome-Wide Association Study RevealsARL15, a Novel Non-HLA Susceptibility Gene for Rheumatoid Arthritis in North Indians

2013 ◽  
Vol 65 (12) ◽  
pp. 3026-3035 ◽  
Author(s):  
Sapna Negi ◽  
Garima Juyal ◽  
Sabyasachi Senapati ◽  
Pushplata Prasad ◽  
Aditi Gupta ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
North Indians

scholarly journals A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease

2011 ◽  
Vol 4 (4) ◽  
pp. 403-412 ◽  
Author(s):  
Philipp S. Wild ◽  
Tanja Zeller ◽  
Arne Schillert ◽  
Silke Szymczak ◽  
Christoph R. Sinning ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome ◽  
Artery Disease

scholarly journals Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1023 ◽  
Author(s):  
Iris ALM van Rooij ◽  
Kerstin U Ludwig ◽  
Julia Welzenbach ◽  
Nina Ishorst ◽  
Michelle Thonissen ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Small Sample ◽  
Genome Wide Association ◽  
P Value ◽  
Genome Wide ◽  
A Genome

Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 × 10−7). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.

scholarly journals Genome-wide association study of individual differences of human lymphocyte profiles using large-scale cytometry data

2020 ◽  
Author(s):  
Daigo Okada ◽  
Naotoshi Nakamura ◽  
Kazuya Setoh ◽  
Takahisa Kawaguchi ◽  
Koichiro Higasa ◽  
...  
Keyword(s):  
Individual Differences ◽  
Association Study ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Cell Classification ◽  
Genome Wide ◽  
A Genome ◽  
Immune Phenotypes ◽  
Human Immune

AbstractHuman immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data.

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