scholarly journals Novel Risk Loci Identified in a Genome-Wide Association Study of Urolithiasis in a Japanese Population

2019 ◽  
Vol 30 (5) ◽  
pp. 855-864 ◽  
Author(s):  
Chizu Tanikawa ◽  
Yoichiro Kamatani ◽  
Chikashi Terao ◽  
Masayuki Usami ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Japanese Population ◽  
Quantitative Traits ◽  
Genetic Factors ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Weighted Genetic Risk Score ◽  
Host Genetic ◽  
Host Genetic Factors

BackgroundA family history of urolithiasis is associated with a more than doubling of urolithiasis risk, and a twin study estimating 56% heritability of the condition suggests a pivotal role for host genetic factors. However, previous genome-wide association studies (GWAS) have identified only six risk-related loci.MethodsTo identify novel urolithiasis-related loci in the Japanese population, we performed a large-scale GWAS of 11,130 cases and 187,639 controls, followed by a replication analysis of 2289 cases and 3817 controls. Diagnosis of urolithiasis was confirmed either by a clinician or using medical records or self-report. We also assessed the association of urolithiasis loci with 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (such as body mass index, lipid storage, eGFR, serum uric acid, and serum calcium), using up to 160,000 samples from BioBank Japan.ResultsThe analysis identified 14 significant loci, including nine novel loci. Ten regions showed a significant association with at least one quantitative trait, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic basis for urolithiasis and these quantitative traits. Four novel loci were related to metabolic traits, obesity, hypertriglyceridemia, or hyperuricemia. The remaining ten loci were associated with kidney- or electrolyte-related traits; these may affect crystallization. Weighted genetic risk score analysis indicated that the highest risk group (top 20%) showed an odds ratio of 1.71 (95% confidence interval, 1.42 to 2.06) - 2.13 (95% confidence interval, 2.00 to 2.27) compared with the reference group (bottom 20%).ConclusionsOur findings provide evidence that host genetic factors related to regulation of metabolic and crystallization pathways contribute to the development of urolithiasis.

scholarly journals A genome-wide association study on meat consumption in a Japanese population: the Japan Multi-Institutional Collaborative Cohort study

2021 ◽  
Vol 10 ◽  
Author(s):  
Yasuyuki Nakamura ◽  
Akira Narita ◽  
Yoichi Sutoh ◽  
Nahomi Imaeda ◽  
Chiho Goto ◽  
...  
Keyword(s):  
Japanese Population ◽  
Genetic Factors ◽  
Association Studies ◽  
Linear Regression Analysis ◽  
Meat Consumption ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
A Genome

Abstract Recent genome-wide association studies (GWAS) on the dietary habits of the Japanese population have shown that an effect rs671 allele was inversely associated with fish consumption, whereas it was directly associated with coffee consumption. Although meat is a major source of protein and fat in the diet, whether genetic factors that influence meat-eating habits in healthy populations are unknown. This study aimed to conduct a GWAS to find genetic variations that affect meat consumption in a Japanese population. We analysed GWAS data using 14 076 participants from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study. We used a semi-quantitative food frequency questionnaire to estimate food intake that was validated previously. Association of the imputed variants with total meat consumption per 1000 kcal energy was performed by linear regression analysis with adjustments for age, sex, and principal component analysis components 1–10. We found that no genetic variant, including rs671, was associated with meat consumption. The previously reported single nucleotide polymorphisms that were associated with meat consumption in samples of European ancestry could not be replicated in our J-MICC data. In conclusion, significant genetic factors that affect meat consumption were not observed in a Japanese population.

scholarly journals GWAS identifies nine nephrolithiasis susceptibility loci related with metabolic metabolic and crystallization pathways

2019 ◽  
Author(s):  
Chizu Tanikawa ◽  
Yoichiro Kamatani ◽  
Chikashi Terao ◽  
Masayuki Usami ◽  
Atsushi Takahashi ◽  
...  
Keyword(s):  
Genetic Background ◽  
Quantitative Traits ◽  
Large Scale ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Genetic Variations ◽  
Susceptibility Loci ◽  
Genome Wide ◽  
Host Genetic ◽  
Host Genetic Factors

ABSTRACTNephrolithiasis is a common urological trait disorder with acute pain. Although previous studies have identified various genetic variations associated with nephrolithiasis, the host genetic factors remain largely unidentified. To identify novel nephrolithiasis loci in the Japanese population, we performed large-scale GWAS (Genome wide association study) using 11,130 cases and 187,639 controls, followed by a replication analysis using 2,289 cases and 3,817 controls. The analysis identified 14 significant loci, including 9 novel loci on 2p23.2-3, 6p21.2, 6p12.3, 6q23.2, 16p12.3, 16q12.2, 17q23.2, 19p13.12, and 20q13.2. Interestingly, 10 of the 14 regions showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits, suggesting a common genetic background among nephrolithiasis patients and these quantitative traits. Four novel loci are related to the metabolic pathway, while the remaining 10 loci are associated with the crystallization pathway. Our findings demonstrate the crucial roles of genetic variations in the development of nephrolithiasis.SIGNIFICANCE STATEMENTNephrolithiasis is a common urothelial disorders with frequent recurrence rate, but its genetic background is largely remained unidentified. Previous GWAS identified 6 genetic factors in total. Here we performed a GWAS using more than 200,000 samples in the Japanese populations, and identified 14 significant loci and nine of them are novel. We also found that 10 of the 14 loci showed a significant association with any of 16 quantitative traits, including metabolic, kidney-related, and electrolyte traits (BMI, eGFR, UA, Ca etc). All 14 significant loci are associate with either metabolic or crystallization pathways. Thus, our findings elucidated the underlying molecular pathogenesis of nephrolithiasis.

scholarly journals Identification of two novel breast cancer loci through large-scale genome-wide association study in the Japanese population

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Siew-Kee Low ◽  
Yoon Ming Chin ◽  
Hidemi Ito ◽  
Keitaro Matsuo ◽  
Chizu Tanikawa ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Risk ◽  
Japanese Population ◽  
Risk Group ◽  
Association Studies ◽  
Genetic Risk Score ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Weighted Genetic Risk Score

AbstractGenome-wide association studies (GWAS) have successfully identified about 70 genomic loci associated with breast cancer. Owing to the complexity of linkage disequilibrium and environmental exposures in different populations, it is essential to perform regional GWAS for better risk prediction. This study aimed to investigate the genetic architecture and to assess common genetic risk model of breast cancer with 6,669 breast cancer patients and 21,930 female controls in the Japanese population. This GWAS identified 11 genomic loci that surpass genome-wide significance threshold of P < 5.0 × 10−8 with nine previously reported loci and two novel loci that include rs9862599 on 3q13.11 (ALCAM) and rs75286142 on 21q22.12 (CLIC6-RUNX1). Validation study was carried out with 981 breast cancer cases and 1,394 controls from the Aichi Cancer Center. Pathway analyses of GWAS signals identified association of dopamine receptor medicated signaling and protein amino acid deacetylation with breast cancer. Weighted genetic risk score showed that individuals who were categorized in the highest risk group are approximately 3.7 times more likely to develop breast cancer compared to individuals in the lowest risk group. This well-powered GWAS is a representative study to identify SNPs that are associated with breast cancer in the Japanese population.

scholarly journals Genome-wide Association Study Identifies New Loci Associated With Risk Of HBV Infection And Disease Progression 

2021 ◽  
Author(s):  
Zheng Zeng ◽  
Liu Hankui ◽  
Xu Huifang ◽  
Lu Haiying ◽  
Yu Yanyan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
East Asian ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Host Genetic ◽  
Host Genetic Factors

Abstract Background: Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes. Results: In order to discover new susceptibility genes for HBV-related outcomes, we conducted a genome-wide association study in 1031 Chinese participants, including 275 HBV clearance subjects, 92 asymptomatic persistence infection carriers (ASPI), 93 chronic hepatitis B patients (CHB), 188 HBV-related decompensated cirrhosis patients (DC), 214 HBV-related hepatocellular carcinoma patients (HCC) and 169 healthy controls (HC). In the case-control study, we observed novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57×10-6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62×10-6; SNP: rs4661093, Gene: ETV3, P = 2.26×10-6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85×10-6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Interestingly, underlying the evolutionary study of HBV-related genes in public database, we found that the derived allele of two HBV clearance related locus, rs3077 and rs9277542, are under strong selection in European population. Conclusions: In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Moreover, we identified two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.

scholarly journals Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Minako Imamura ◽  
Atsushi Takahashi ◽  
Toshimasa Yamauchi ◽  
Kazuo Hara ◽  
Kazuki Yasuda ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Japanese Population ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Genome Wide

scholarly journals Genome-wide association studies and heritability analysis reveal the involvement of host genetics in the Japanese gut microbiota

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Sachiko Ishida ◽  
Kumiko Kato ◽  
Masami Tanaka ◽  
Toshitaka Odamaki ◽  
Ryuichi Kubo ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Microbiota Composition ◽  
Intrinsic Factors ◽  
Genome Wide ◽  
Gut Microbiota Composition

AbstractNumerous host extrinsic and intrinsic factors affect the gut microbiota composition, but their cumulative effects do not sufficiently explain the variation in the microbiota, suggesting contributions of missing factors. The Japanese population possesses homogeneous genetic features suitable for genome-wide association study (GWAS). Here, we performed GWASs for human gut microbiota using 1068 healthy Japanese adults. To precisely evaluate genetic effects, we corrected for the impacts of numerous host extrinsic and demographic factors by introducing them as covariates, enabling us to discover five loci significantly associated with microbiome diversity measures: HS3ST4, C2CD2, 2p16.1, 10p15.1, and 18q12.2. Nevertheless, these five variants explain only a small fraction of the variation in the gut microbiota. We subsequently investigated the heritability of each of the 21 core genera and found that the abundances of six genera are heritable. We propose that the gut microbiota composition is affected by a highly polygenic architecture rather than several strongly associated variants in the Japanese population.

scholarly journals 12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Ryo Takata ◽  
Atsushi Takahashi ◽  
Masashi Fujita ◽  
Yukihide Momozawa ◽  
Edward J. Saunders ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Japanese Population ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
European Population ◽  
Genome Wide Association ◽  
High Risk Population ◽  
Genome Wide Association Studies ◽  
Susceptibility Loci ◽  
Genome Wide

Abstract Genome-wide association studies (GWAS) have identified ~170 genetic loci associated with prostate cancer (PCa) risk, but most of them were identified in European populations. We here performed a GWAS and replication study using a large Japanese cohort (9,906 cases and 83,943 male controls) to identify novel susceptibility loci associated with PCa risk. We found 12 novel loci for PCa including rs1125927 (TMEM17, P = 3.95 × 10−16), rs73862213 (GATA2, P = 5.87 × 10−23), rs77911174 (ZMIZ1, P = 5.28 × 10−20), and rs138708 (SUN2, P = 1.13 × 10−15), seven of which had crucially low minor allele frequency in European population. Furthermore, we stratified the polygenic risk for Japanese PCa patients by using 82 SNPs, which were significantly associated with Japanese PCa risk in our study, and found that early onset cases and cases with family history of PCa were enriched in the genetically high-risk population. Our study provides important insight into genetic mechanisms of PCa and facilitates PCa risk stratification in Japanese population.

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