Meta-analysis of genome-wide association studies for panic disorder in the Japanese population

AbstractAlzheimer’s disease (AD) has no cure, but early detection and risk prediction could allow earlier intervention. Genetic risk factors may differ between ethnic populations. To discover novel susceptibility loci of AD in the Japanese population, we conducted a genome-wide association study (GWAS) with 3962 AD cases and 4074 controls. Out of 4,852,957 genetic markers that passed stringent quality control filters, 134 in nine loci, including APOE and SORL1, were convincingly associated with AD. Lead SNPs located in seven novel loci were genotyped in an independent Japanese AD case–control cohort. The novel locus FAM47E reached genome-wide significance in a meta-analysis of association results. This is the first report associating the FAM47E locus with AD in the Japanese population. A trans-ethnic meta-analysis combining the results of the Japanese data sets with summary statistics from stage 1 data of the International Genomics of Alzheimer’s Project identified an additional novel susceptibility locus in OR2B2. Our data highlight the importance of performing GWAS in non-European populations.

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Replication Study in a Japanese Population of Six Susceptibility Loci for Type 2 Diabetes Originally Identified by a Transethnic Meta-Analysis of Genome-Wide Association Studies

PLoS ONE ◽

10.1371/journal.pone.0154093 ◽

2016 ◽

Vol 11 (4) ◽

pp. e0154093 ◽

Cited By ~ 6

Author(s):

Ren Matsuba ◽

Minako Imamura ◽

Yasushi Tanaka ◽

Minoru Iwata ◽

Hiroshi Hirose ◽

...

Keyword(s):

Type 2 Diabetes ◽

Japanese Population ◽

Association Studies ◽

Meta Analysis ◽

Replication Study ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Susceptibility Loci ◽

Genome Wide

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Genome-wide association meta-analysis identifies novel GP2 gene risk variants for pancreatic cancer in the Japanese population

10.1101/498659 ◽

2018 ◽

Author(s):

Yingsong Lin ◽

Masahiro Nakatochi ◽

Hidemi Ito ◽

Yoichiro Kamatani ◽

Akihito Inoko ◽

...

Keyword(s):

Pancreatic Cancer ◽

Japanese Population ◽

Cancer Susceptibility ◽

Association Studies ◽

Meta Analysis ◽

Functional Characterization ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Gene Variants ◽

Genome Wide

AbstractThe etiology of pancreatic cancer remains largely unknown. Here, we report the results of a meta-analysis of three genome-wide association studies (GWASs) comprising 2,039 pancreatic cancer cases and 32,592 controls, the largest sample size in the Japanese population. We identified 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P<5.0×10-8) and 4 suggestive loci (P<1.0×10-6) for pancreatic cancer. Of these risk loci, 16p12.3 is novel; the lead SNP maps to rs78193826 (odds ratio (OR)=1.46, 95% CI=1.29-1.66, P=4.28×10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant predicted to be highly deleterious. Additionally, the gene-based GWAS identified a novel gene, KRT8, which is linked to exocrine pancreatic and liver diseases. The identified GP2 gene variants were pleiotropic for multiple traits, including type 2 diabetes, hemoglobin A1c (HbA1c) levels, and pancreatic cancer. Mendelian randomization analyses corroborated causality between HbA1c and pancreatic cancer. These findings suggest that GP2 gene variants are associated with pancreatic cancer susceptibility in the Japanese population, prompting further functional characterization of this locus.

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Metanalysis of genome-wide association studies for panic disorder suggest pathways and mechanisms of pathogenesis

10.1101/326017 ◽

2018 ◽

Author(s):

Rhayra Xavier do Carmo Silva ◽

Sueslene Prado Rocha ◽

Dainara Pereira dos Santos Souza ◽

Monica Gomes Lima-Maximino ◽

Caio Maximino

Keyword(s):

Panic Disorder ◽

Inflammatory Responses ◽

Drug Repositioning ◽

Association Studies ◽

Meta Analysis ◽

Genome Wide Association ◽

Mouse Strains ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genome Wide

AbstractPanic disorder (PD) is characterized by abrupt surges of intense fear and distress. There is evidence for a genetic component in this disorder. We ran a meta-analysis of genome-wide association studies of patients with PD, and found 25 single-nucleotide polymorphisms that were associated with the disorder. Causal gene prediction based on these polymorphisms uncovered 20 hits. Exploratory analyses suggested that these genes formed interactor networks, which was enriched in signaling pathways associated with immune and inflammatory responses, as well as growth factors and other developmental mediators. A subset of genes is enriched in limbic regions of the human brain and in microglia and myelinating oligodendrocytes of mice. While these genes were not associated with relevant neurobehavioral phenotypes in mutant mice, expression levels of several causal genes in the amygdala, prefrontal cortex, hippocampus, hypothalamus, and adrenal gland of recombinant mouse strains was associated with endophenotypes of fear conditioning. Drug repositioning prediction was unsuccessful, but this does not discard these genes and pathways as targets for investigational drugs. In general,ASB3,EIF2S2, RASGRF2, andTRMT2B(and its coded proteins) emerged as interesting targets for mechanistic research on PD. These exploratory findings point towards hypotheses of pathogenesis and neuropharmacology that need to be further investigated.

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Faculty Opinions recommendation of Meta-Analysis of Genome-Wide Association Studies and Network Analysis-Based Integration with Gene Expression Data Identify New Suggestive Loci and Unravel a Wnt-Centric Network Associated with Dupuytren's Disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726582766.793522025 ◽

2016 ◽

Author(s):

Rik Lories

Keyword(s):

Gene Expression ◽

Network Analysis ◽

Gene Expression Data ◽

Association Studies ◽

Meta Analysis ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Expression Data ◽

Dupuytren's Disease ◽

Genome Wide

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Genome-Wide Association Studies Identify Two Novel Loci Conferring Susceptibility to Diabetic Retinopathy in Japanese Patients with Type 2 Diabetes

Human Molecular Genetics ◽

10.1093/hmg/ddab044 ◽

2021 ◽

Author(s):

Minako Imamura ◽

Atsushi Takahashi ◽

Masatoshi Matsunami ◽

Momoko Horikoshi ◽

Minoru Iwata ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Retinopathy ◽

Association Studies ◽

Meta Analysis ◽

Japanese Patients ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Stage 1

Abstract Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases, and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (p < 1.0 × 10−4) in an independent case–control study (Stage-2, 2260 cases and 723 controls). After combining the association data (Stage-1 and -2) using meta-analysis, the associations of two loci reached a genome-wide significance level: rs12630354 near STT3B on chromosome 3, p = 1.62 × 10−9, odds ratio (OR) = 1.17, 95% confidence interval (CI) 1.11–1.23, and rs140508424 within PALM2 on chromosome 9, p = 4.19 × 10−8, OR = 1.61, 95% CI 1.36–1.91. However, the association of these two loci were not replicated in Korean, European, or African American populations. Gene-based analysis using Stage-1 GWAS data identified a gene-level association of EHD3 with susceptibility to diabetic retinopathy (p = 2.17 × 10−6). In conclusion, we identified two novel SNP loci, STT3B and PALM2, and a novel gene, EHD3, that confers susceptibility to diabetic retinopathy; however, further replication studies are required to validate these associations.

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A meta-analysis of genome-wide association studies for average daily gain and lean meat percentage in two Duroc pig populations

BMC Genomics ◽

10.1186/s12864-020-07288-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shenping Zhou ◽

Rongrong Ding ◽

Fanming Meng ◽

Xingwang Wang ◽

Zhanwei Zhuang ◽

...

Keyword(s):

Candidate Genes ◽

Growth And Development ◽

Genetic Architecture ◽

Association Studies ◽

Meta Analysis ◽

Average Daily Gain ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Daily Gain

Abstract Background Average daily gain (ADG) and lean meat percentage (LMP) are the main production performance indicators of pigs. Nevertheless, the genetic architecture of ADG and LMP is still elusive. Here, we conducted genome-wide association studies (GWAS) and meta-analysis for ADG and LMP in 3770 American and 2090 Canadian Duroc pigs. Results In the American Duroc pigs, one novel pleiotropic quantitative trait locus (QTL) on Sus scrofa chromosome 1 (SSC1) was identified to be associated with ADG and LMP, which spans 2.53 Mb (from 159.66 to 162.19 Mb). In the Canadian Duroc pigs, two novel QTLs on SSC1 were detected for LMP, which were situated in 3.86 Mb (from 157.99 to 161.85 Mb) and 555 kb (from 37.63 to 38.19 Mb) regions. The meta-analysis identified ten and 20 additional SNPs for ADG and LMP, respectively. Finally, four genes (PHLPP1, STC1, DYRK1B, and PIK3C2A) were detected to be associated with ADG and/or LMP. Further bioinformatics analysis showed that the candidate genes for ADG are mainly involved in bone growth and development, whereas the candidate genes for LMP mainly participated in adipose tissue and muscle tissue growth and development. Conclusions We performed GWAS and meta-analysis for ADG and LMP based on a large sample size consisting of two Duroc pig populations. One pleiotropic QTL that shared a 2.19 Mb haplotype block from 159.66 to 161.85 Mb on SSC1 was found to affect ADG and LMP in the two Duroc pig populations. Furthermore, the combination of single-population and meta-analysis of GWAS improved the efficiency of detecting additional SNPs for the analyzed traits. Our results provide new insights into the genetic architecture of ADG and LMP traits in pigs. Moreover, some significant SNPs associated with ADG and/or LMP in this study may be useful for marker-assisted selection in pig breeding.

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