Short or Long Sleep Duration and CKD: A Mendelian Randomization Study

et al. 2021

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BackgroundBidirectional association between atrial fibrillation (AF) and cancer was reported by observational investigations. Additional study is warranted to investigate the causal effects of AF on risk of cancer.MethodsThis study was a summary-level Mendelian randomization (MR) analysis. Genetic instrument for AF was developed from a genome-wide association study (GWAS) meta-analysis for AF including 537,409 European ancestry individuals including 55,144 AF cases. The outcome data for risk of 17 site-specific cancer from a previous GWAS meta-analysis of the UK Biobank (48,961/359,825 case/controls) and Genetic Epidemiology Research on Adult Health and Aging (16,001/50,525 case/controls) cohorts including European ancestry individuals was investigated. Inverse variance weighted method was the main MR method, supported by pleiotropy-robust sensitivity analysis including MR-Egger regression and penalized weighted median method.ResultsThe causal estimates indicated that AF was causally linked to higher risk of cancers of lung, breast, cervix, endometrium, and melanoma. MR-Egger test for directional pleiotropy indicated absence of a pleiotropy in the identified causal estimates and MR-Egger regression and median-based methods provided similarly significant findings. On the other hand, the genetic predisposition of AF was significantly associated with lower risk of esophagus/gastric cancer, but possibility of a directional pleiotropy remained in the association.ConclusionsAF is a causal factor for certain types of cancer. Appropriate cancer screening should be suggested in clinical guidelines for AF patients. Future trial is necessary to confirm whether appropriate management of AF may reduce the risk of cancer which is a major cause of deaths in AF patients.

Section: Methodsmentioning

confidence: 99%

Reverse causal effect of atrial fibrillation on 17 site-specific cancer risk: A Mendelian randomization study

et al. 2021

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“…In the analysis, we included 337,138 white British UK Biobank participants passing the sample quality control. 11 Among them, 274,353 individuals had available information for baseline eGFR values by the CKD-EPI equation based on serum creatinine values and adjusted clinical covariates. Multivariable linear regression analysis was performed for the eGFR values with the exposure of the minor alleles of rs738409 or rs13107325, with the exposure effect size for NAFLD or cT1 value introduced from previous GWAS studies.…”

Section: Methodsmentioning

confidence: 99%

“…In addition, with the availability of large-scale genetic data for kidney function traits, MR has been utilized to identify causal risk factors for kidney function impairment. [10][11][12] In this MR study, we performed MR analysis by selecting rs738409 as a genetic instrument to predict NAFLD and assess its association with kidney function outcome in two independent, population-scale genetic datasets for kidney function traits. We also introduced an alternate genetic instrument, the rs13107325 SNP, which is strongly associated with the liver MRI corrected T1 (cT1) score, which is a marker of steatohepatitis and liver fibrosis, 13 to support the causal linkage between NAFLD and kidney function.…”

Section: Introductionmentioning

confidence: 99%

Causal effects from non-alcoholic fatty liver disease on kidney function: A Mendelian randomization study

et al. 2021

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Background & aims: An observational association between nonalcoholic fatty liver disease (NAFLD) and kidney function impairment has been reported. A genetic variant linked to an increased risk of NAFLD, the G allele of rs738409, has been reported to be associated with a reduction in estimated glomerular filtration rate (eGFR). Methods: In this Mendelian randomization (MR) study, we selected rs738409 as a genetic instrument to predict NAFLD. The genetic variant rs13107325, which is strongly associated with the steatohepatitis marker liver MRI corrected T1 score, was introduced as an alternate genetic instrument for the NAFLD-related phenotype. The eGFR outcome was assessed in individuals of white British ancestry included in the UK Biobank (N = 321,260), and associations adjusted for major metabolic disorder and income grades were investigated. Further, the associations were reassessed in two negative control subgroups (body mass index < 25 kg/m2 and serum alanine aminotransferase level < 20 IU/mL) with a low probability of developing NAFLD. As a replication analysis, a summary-level MR was performed with the European ancestry CKDGen dataset (N = 567,460). Results: In the UK Biobank dataset, a genetic predisposition for NAFLD or an increased liver T1 score was significantly associated with a reduced eGFR with adjustment for major metabolic disorders. Although the associations were not significant in the negative control subgroups with a low probability of developing NAFLD, they were significant in the subgroups with a remaining risk of NAFLD, suggesting the absence of a horizontal pleiotropic pathway. The summary-level MR from the CKDGen dataset supported the causal effects of NAFLD on reduced eGFR. Conclusions: This MR analysis supports the causal reduction in eGFR by NAFLD.

“…MR has been implemented in the medical literature and has identified important causal factors for the risk of CAD or other chronic comorbidities. [15][16][17][18] In this study, we aimed to investigate the causal effects of serum n-3 and n-6 PUFA levels on the risk of CAD by MR analysis testing the association between genetic predisposition for each PUFA type and the risk of CAD or myocardial infarction (MI). We performed both allele-score-based MR by individual-level data and MR based on summary-level data in different cohorts to replicate the findings.…”

Section: Introductionmentioning

confidence: 99%

“…MR has been implemented in the medical literature and has identified important causal factors for the risk of CAD or other chronic comorbidities. 15-18…”

Section: Introductionmentioning

confidence: 99%

Causal effects of serum levels of n-3 or n-6 polyunsaturated fatty acids on coronary artery disease: Mendelian randomization study

et al. 2020

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BackgroundAdditional studies on the causal effects of 3-n and 6-n polyunsaturated fatty acids (PUFAs) on the risk of coronary artery disease (CAD) are warranted.MethodsThis Mendelian randomization (MR) study utilized a genetic instrument developed from previous genome-wide association studies for various serum 3-n and 6-n PUFA levels. First, we calculated the allele scores for genetic predisposition of PUFAs in individuals of European ancestry in the UK Biobank data (N=337,129). The allele score-based MR was obtained by regressing the allele scores to CAD risks. Second, summary-level MR was performed with the CARDIoGRAMplusC4D data for CAD (N=184,305). The inverse variance-weighted or Wald ratio method was the main analysis for the summary-level MR, and when multiple single nucleotide polymorphisms were utilized (e.g., linoleic acid), MR-Egger and weighted median methods were implemented as sensitivity analyses.ResultsHigher genetically predicted eicosapentaenoic acid and dihomo-gamma-linolenic acid levels were significantly associated with a lower risk of CAD both in the allele-score-based and summary-level MR analyses. Higher allele scores for linoleic acid level were significantly associated with lower CAD risks, and in the summary-level MR, the causal estimates by the MR-Egger and weighted median methods also indicated that higher linoleic acid levels cause a lower risk of CAD. Arachidonic acid was the 6-n PUFA that showed significant causal estimates for a higher risk of CAD. Higher docosapentaenoic acid and adrenic acid levels showed inconsistent findings in the MR analysis results.ConclusionsThis study supports the causal effects of certain 3-n and 6-n PUFA types on the risk of CAD.