Mendelian Randomization on hs-CRP and eGFR
Fujii, Ryosuke Nagoya University|Fujita Health University
Hishida, Asahi Nagoya University
Nishiyama, Takeshi Nagoya City University
Nakatochi, Masahiro Nagoya University
Matsuo, Keitaro Aichi Cancer Center|Nagoya University
Ito, Hidemi Aichi Cancer Center
Nishida, Yuichiro Saga University
Shimanoe, Chisato Saga University
Nakamura, Yasuyuki Shiga University of Medical Science
Turin, Tanvir Chowdhury Shiga University of Medical Science|University of Calgary
Suzuki, Sadao Nagoya City University
Watanabe, Miki Nagoya City University
Ibusuki, Rie Kagoshima University
Takezaki, Toshiro Kagoshima University
Mikami, Haruo Chiba Cancer Center Research Institute
Nakamura, Yohko Chiba Cancer Center Research Institute
Ikezaki, Hiroaki Kyushu University
Murata, Masayuki Kyushu University
Kuriki, Kiyonori University of Shizuoka
Kuriyama, Nagato Kyoto Prefectural University of Medicine
Matsui, Daisuke Kyoto Prefectural University of Medicine
Tsukamoto, Mineko Nagoya University
Tamura, Takashi Nagoya University
Kubo, Yoko Nagoya University
Kondo, Takaaki Nagoya University
Momozawa, Yukihide RIKEN
Kubo, Michiaki RIKEN
Takeuchi, Kenji Nagoya University
Wakai, Kenji Nagoya University
Mendelian randomization study
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.
Journal of Epidemiology
Japan Epidemiological Association
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