著者
Mako Nagayoshi Asahi Hishida Tomonori Shimizu Yasufumi Kato Yoko Kubo Rieko Okada Takashi Tamura Jun Otonari Hiroaki Ikezaki Megumi Hara Yuichiro Nishida Isao Oze Yuriko N. Koyanagi Yohko Nakamura Miho Kusakabe Rie Ibusuki Keiichi Shibuya Sadao Suzuki Takeshi Nishiyama Teruhide Koyama Etsuko Ozaki Kiyonori Kuriki Naoyuki Takashima Yasuyuki Nakamura Sakurako Katsuura-Kamano Kokichi Arisawa Masahiro Nakatochi Yukihide Momozawa Kenji Takeuchi Kenji Wakai
出版者
Japan Epidemiological Association
雑誌
Journal of Epidemiology (ISSN:09175040)
巻号頁・発行日
pp.JE20220154, (Released:2023-01-28)
参考文献数
54

Background: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated.Methods: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study, and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses by the two-stage least squares estimator method. The β-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses.Results: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with higher risks of higher blood pressure, triglycerides, uric acid, lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent by different methods, including the directions.Conclusions: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.
著者
Kazuhiro MAEDA Mai INOUE Miho TANAKA Yukihide MOMOZAWA
出版者
JAPANESE SOCIETY OF VETERINARY SCIENCE
雑誌
Journal of Veterinary Medical Science (ISSN:09167250)
巻号頁・発行日
pp.18-0485, (Released:2019-02-12)
被引用文献数
4

Patellar luxation (PL) is one of the most common orthopedic disorders in dogs and a genetic factor is considered to play an important role in the development of PL. Genomic analysis has attempted to identify the genetic markers associated with the development of PL but only suggestive markers have been identified. Carefully selecting breeds with higher incidence rates of congenital PL as well as affected dogs with more severe symptoms are required, but such information remains limited to date. This study aimed to assess the genetic contribution to the development of PL in puppies. Using data on PL from 2,048 puppies of the nine common breeds in Japan, the association of PL grades between the limbs, breed, and sex as well as the concordance of PL between littermates were examined. A significant correlation was found between right and left limbs in PL grades in all the puppies (Spearman rank correlation coefficient (rs)=0.91, P<0.001) and for each breed (rs=0.81–0.93, P<0.001). In total, 20.3% of the puppies were affected. The inter-breed difference in PL prevalence was 2.1–38.1%, and Toy Poodles showed the highest prevalence rates. Littermates of the affected puppies with PL grade ≥2 had a 16.2-fold higher risk (P<0.001). Thus, these results suggest that PL in puppies is primarily influenced by genetics, especially in Toy Poodles. These data highlight the necessity of using a breeding scheme to decrease the prevalence of PL.
著者
Mineko Tsukamoto Asahi Hishida Takashi Tamura Mako Nagayoshi Rieko Okada Yoko Kubo Yasufumi Kato Nobuyuki Hamajima Yuichiro Nishida Chisato Shimanoe Rie Ibusuki Kenichi Shibuya Naoyuki Takashima Yasuyuki Nakamura Miho Kusakabe Yohko Nakamura Yuriko N. Koyanagi Isao Oze Takeshi Nishiyama Sadao Suzuki Isao Watanabe Daisuke Matsui Jun Otonari Hiroaki Ikezaki Sakurako Katsuura-Kamano Kokichi Arisawa Kiyonori Kuriki Masahiro Nakatochi Yukihide Momozawa Kenji Takeuchi Kenji Wakai Keitaro Matsuo
出版者
Japan Epidemiological Association
雑誌
Journal of Epidemiology (ISSN:09175040)
巻号頁・発行日
pp.JE20220341, (Released:2023-07-29)
参考文献数
72

Background: The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites as well as to detect related gene-environment interactions in Japanese.Methods: We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B12 (VB12) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed.Results: For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5×10-8). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB12. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity > 33% on Hcy (β = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and < 0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (β = 0.033, P = 0.048).Conclusions: The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized CVD prevention.
著者
Ryosuke Fujii Asahi Hishida Takeshi Nishiyama Masahiro Nakatochi Keitaro Matsuo Hidemi Ito Yuichiro Nishida Chisato Shimanoe Yasuyuki Nakamura Tanvir Chowdhury Turin Sadao Suzuki Miki Watanabe Rie Ibusuki Toshiro Takezaki Haruo Mikami Yohko Nakamura Hiroaki Ikezaki Masayuki Murata Kiyonori Kuriki Nagato Kuriyama Daisuke Matsui Kokichi Arisawa Sakurako Katsuura-Kamano Mineko Tsukamoto Takashi Tamura Yoko Kubo Takaaki Kondo Yukihide Momozawa Michiaki Kubo Kenji Takeuchi Kenji Wakai
出版者
Japan Epidemiological Association
雑誌
Journal of Epidemiology (ISSN:09175040)
巻号頁・発行日
vol.32, no.11, pp.483-488, 2022-11-05 (Released:2022-11-05)
参考文献数
38

Background: Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches.Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively.Results: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval [CI], −0.019 to 0.020 and −0.003; 95% CI, −0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 0.005; 95% CI, −0.020 to 0.010 and −0.004; 95% CI, −0.020 to 0.012, respectively). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: −0.008; 95% CI, −0.058 to 0.042; IVAsian: 0.001; 95% CI, −0.036 to 0.036).Conclusion: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.
著者
Ryosuke Fujii Asahi Hishida Takeshi Nishiyama Masahiro Nakatochi Keitaro Matsuo Hidemi Ito Yuichiro Nishida Chisato Shimanoe Yasuyuki Nakamura Tanvir Chowdhury Turin Sadao Suzuki Miki Watanabe Rie Ibusuki Toshiro Takezaki Haruo Mikami Yohko Nakamura Hiroaki Ikezaki Masayuki Murata Kiyonori Kuriki Nagato Kuriyama Daisuke Matsui Kokichi Arisawa Sakurako Katsuura-Kamano Mineko Tsukamoto Takashi Tamura Yoko Kubo Takaaki Kondo Yukihide Momozawa Michiaki Kubo Kenji Takeuchi Kenji Wakai
出版者
Japan Epidemiological Association
雑誌
Journal of Epidemiology (ISSN:09175040)
巻号頁・発行日
pp.JE20200540, (Released:2021-02-20)
参考文献数
38

Background: Inflammation is thought to be a risk factor for kidney disease. However, discussion is controversial whether inflammatory status is either a cause or an outcome of chronic kidney disease. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using mendelian randomization (MR) approaches.Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively.Results: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 95%CI: 0.000, –0.019 to 0.020 and –0.003, –0.019 to 0.014). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 95% CI: –0.005, –0.020 to 0.010 and –0.004, –0.020 to 0.012). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: –0.008, –0.058 to 0.042; IVAsian: 0.001, –0.036 to 0.036).Conclusions: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.