Abstract Background Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested...

Additional file 3: Supplementary Table 1. Characteristics of the study participants with information for cognition outcomes. Mean and SD are shown for continuous variables. Supplementary Table 2. Characteristics of the study participants with information for neuroimaging outcomes. Mean and SD are shown for continuous variables. Supplementary Table 3. Characteristics of the study participants with information for CSF biomarkers. Mean and SD are shown for continuous variables.

Additional file 5: Supplementary Figure 1. Leave-one-out permutation analysis plot for AD signature among individuals at high genetic predisposition to AD obtained by leaving out the SNP indicated and repeating the Inverse-Variance Weighted method with the rest of the instrumental variables. Supplementary Figure 2. Leave-one-out permutation analysis plot for Aging signature among individuals at high genetic predisposition to AD, obtained by leaving out the SNP indicated and repeating the Inverse-Variance Weighted method with the rest...

Abstract Background Hemodialysis (HD) patients with atrial fibrillation (AF) have a particularly high risk of stroke and bleeding, but no high-quality evidence-based recommendations exist to properly manage these patients. Objectives We aim to evaluate the ischemic versus the hemorrhagic risk in a HD population with AF. Methods We selected incident patients that started hemodialysis between 2011 and 2015. All patients that had AF before HD, or developed AF during the follow-up, were included. Both CHA2DS2...

Additional file 1: Additional figures and tables.

Additional file 1. Supplementary material regarding (i) the definition of cancer cases for HCC, GBC, Adv.PrC and Loc.PrC; (ii) the definition and implementation of the data-shared lasso; (iii) the models used to derive point estimates and confidence intervals from the model selected by the data-shared lasso; and (iv) the univariate analysis conducted for comparison.

Abstract Background Epidemiological studies of associations between metabolites and cancer risk have typically focused on specific cancer types separately. Here, we designed a multivariate pan-cancer analysis to identify metabolites potentially associated with multiple cancer types, while also allowing the investigation of cancer type-specific associations. Methods We analysed targeted metabolomics data available for 5828 matched case-control pairs from cancer-specific case-control studies on breast, colorectal, endometrial, gallbladder, kidney, localized and advanced prostate cancer, and hepatocellular carcinoma nested...

Additional file 2: Supplementary tables and figures. Figure S1. Pearson correlation between the 117 original metabolites. Figure S2. Sensitivity analyses of mutually adjusted ORs for the overall associations and cancer type-specific deviations. Figure S3. Sensitivity analysis of mutually adjusted ORs for the overall associations and cancer type-specific deviations with or without excluding hormone users. Figure S4. p-values of tests for departure from linearity and effect modification by BMI. Figure S5. ORs for the overall associations...

Abstract Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer’s disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance, N = 2233; brain age and AD-related signatures, N = 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N = 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the...

Additional file 1: Supplementary Table 1. Characteristics of Single Nucleotide Polymorphisms (SNPs) associated with longer telomere length. The effect allele refers to the allele that is associated with longer telomere length. Chromosomal position of the SNPs (genome assembly GRCh37 (hg19)) according to the public archive for genetic variation within and across different species developed and hosted by the National Center for Biotechnology Information (NCBI) in collaboration with the National Human Genome Research Institute (NHGRI) (dbSNP).

Additional file 4: Supplementary Table 1. Results of the effect of genetically predicted longer telomere length on AD endophenotypes in the entire sample. Supplementary Table 2. Results of the effect of genetically predicted longer telomere length on AD endophenotypes among APOE-ɛ4 carriers. Supplementary Table 3. Results of the effect of genetically predicted longer telomere length on AD endophenotypes among APOE-ɛ4 non-carriers. Supplementary Table 4. Results of the effect of genetically predicted longer telomere length on...

Additional file 5: Supplementary Figure 1. Leave-one-out permutation analysis plot for AD signature among individuals at high genetic predisposition to AD obtained by leaving out the SNP indicated and repeating the Inverse-Variance Weighted method with the rest of the instrumental variables. Supplementary Figure 2. Leave-one-out permutation analysis plot for Aging signature among individuals at high genetic predisposition to AD, obtained by leaving out the SNP indicated and repeating the Inverse-Variance Weighted method with the rest...

Additional file 2: Original data for calculations in the manuscript.

Additional file 2: Original data for calculations in the manuscript.

Additional file 1: Supplementary Table 1. Characteristics of Single Nucleotide Polymorphisms (SNPs) associated with longer telomere length. The effect allele refers to the allele that is associated with longer telomere length. Chromosomal position of the SNPs (genome assembly GRCh37 (hg19)) according to the public archive for genetic variation within and across different species developed and hosted by the National Center for Biotechnology Information (NCBI) in collaboration with the National Human Genome Research Institute (NHGRI) (dbSNP).

Additional file 2: Supplementary Table 1. Linear regression estimates for cognition outcomes in the entire sample. All models are adjusted for covariates: age, sex, education, and APOE status. Supplementary Table 2. Linear regression estimates for neuroimaging outcomes (i.e., Alzheimer’s disease and aging signatures) outcome in the entire sample. All models are adjusted for covariates: age, sex, education, and APOE status. Supplementary Table 3. Linear regression estimates for CSF biomarkers outcomes in the entire sample. All...

Additional file 2: Supplementary Table 1. Linear regression estimates for cognition outcomes in the entire sample. All models are adjusted for covariates: age, sex, education, and APOE status. Supplementary Table 2. Linear regression estimates for neuroimaging outcomes (i.e., Alzheimer’s disease and aging signatures) outcome in the entire sample. All models are adjusted for covariates: age, sex, education, and APOE status. Supplementary Table 3. Linear regression estimates for CSF biomarkers outcomes in the entire sample. All...

Additional file 4: Supplementary Table 1. Results of the effect of genetically predicted longer telomere length on AD endophenotypes in the entire sample. Supplementary Table 2. Results of the effect of genetically predicted longer telomere length on AD endophenotypes among APOE-ɛ4 carriers. Supplementary Table 3. Results of the effect of genetically predicted longer telomere length on AD endophenotypes among APOE-ɛ4 non-carriers. Supplementary Table 4. Results of the effect of genetically predicted longer telomere length on...

Additional file 2: Supplementary tables and figures. Figure S1. Pearson correlation between the 117 original metabolites. Figure S2. Sensitivity analyses of mutually adjusted ORs for the overall associations and cancer type-specific deviations. Figure S3. Sensitivity analysis of mutually adjusted ORs for the overall associations and cancer type-specific deviations with or without excluding hormone users. Figure S4. p-values of tests for departure from linearity and effect modification by BMI. Figure S5. ORs for the overall associations...

Abstract Background Hemodialysis (HD) patients with atrial fibrillation (AF) have a particularly high risk of stroke and bleeding, but no high-quality evidence-based recommendations exist to properly manage these patients. Objectives We aim to evaluate the ischemic versus the hemorrhagic risk in a HD population with AF. Methods We selected incident patients that started hemodialysis between 2011 and 2015. All patients that had AF before HD, or developed AF during the follow-up, were included. Both CHA2DS2...

Abstract Telomere length (TL) is associated with biological aging, consequently influencing the risk of age-related diseases such as Alzheimer’s disease (AD). We aimed to evaluate the potential causal role of TL in AD endophenotypes (i.e., cognitive performance, N = 2233; brain age and AD-related signatures, N = 1134; and cerebrospinal fluid biomarkers (CSF) of AD and neurodegeneration, N = 304) through a Mendelian randomization (MR) analysis. Our analysis was conducted in the context of the...

Additional file 3: Supplementary Table 1. Characteristics of the study participants with information for cognition outcomes. Mean and SD are shown for continuous variables. Supplementary Table 2. Characteristics of the study participants with information for neuroimaging outcomes. Mean and SD are shown for continuous variables. Supplementary Table 3. Characteristics of the study participants with information for CSF biomarkers. Mean and SD are shown for continuous variables.

Additional file 1: Additional figures and tables.

Additional file 1. Supplementary material regarding (i) the definition of cancer cases for HCC, GBC, Adv.PrC and Loc.PrC; (ii) the definition and implementation of the data-shared lasso; (iii) the models used to derive point estimates and confidence intervals from the model selected by the data-shared lasso; and (iv) the univariate analysis conducted for comparison.

Abstract Background Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients. Results The...