Abstract Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose this study is clarify time-dependent effects between long-term oral cancer risk. We performed an observational in 256,661 women from UK Biobank, born 1939 1970. Information on diagnoses were collected self-reported data national registers until March 2019. Cumulative over timespan study, as measured by OR, instantaneous risk, HR, assessed using Logistic Cox...

Estradiol is the primary female sex hormone and plays an important role for skeletal health in both sexes. Several enzymes are involved estradiol metabolism, but few genome-wide association studies (GWAS) have been performed to characterize genetic contribution variation estrogen levels.Identify loci affecting levels estimate causal effect of on bone mineral density (BMD).We GWAS males (n = 147 690) females 163 985) from UK Biobank. was analyzed as a binary phenotype above/below detection...

Obesity is associated with several types of cancer and fat distribution, which differs dramatically between sexes, has been suggested to be an independent risk factor. However, sex-specific effects on have rarely studied. Here we estimate the accumulation distribution in females males. We performed a prospective study 442,519 UK Biobank participants, for 19 additional histological subtypes, mean follow-up time 13.4 years. Cox proportional hazard models were used effect 14 different adiposity...

Abstract Genome-wide association studies (GWAS) have identified associations between thousands of common genetic variants and human traits. However, usually explain a limited fraction the heritability trait. A powerful resource for identifying trait-associated is whole genome sequencing (WGS) data in cohorts comprised families or individuals from geographical area. To evaluate power WGS compared to imputations, we performed GWAS on 72 inflammatory biomarkers, kinship-structured cohort. When...

Many disease-associated protein biomarkers protect against disease development.

High levels of estrogen are associated with increased risk breast and endometrial cancer have been suggested to also play a role in the development ovarian cancer. Cancerogenic effects estradiol, most prominent form estrogen, highlighted as side effect estrogen-only menopausal hormone therapy. However, whether high endogenous estrogens, produced within body, promote development, has not fully established.We aimed examine causal estradiol on breast, endometrial, cancer.Here we performed...

Understanding how genetic variants drive phenotypic differences is a major challenge in molecular biology. Single nucleotide polymorphisms form the vast majority of variation and play critical roles complex, polygenic phenotypes, yet their functional impact poorly understood from traditional gene-level analyses. In-depth knowledge on single has broad applications health disease, population genomic or evolution studies. The wealth data available tools make Drosophila melanogaster an ideal...

Abstract Despite the success of genome-wide association studies, much genetic contribution to complex traits remains unexplained. Here, we analyse high coverage whole-genome sequencing data, evaluate rare variants 414 plasma proteins. The frequency distribution is skewed towards spectrum, and damaging are more often rare. We estimate that less than 4.3% narrow-sense heritability expected be explained by in our cohort. Using a gene-based approach, identify Cis -associations for 237 proteins,...

IntroductionDeep vein thrombosis (DVT) is a complex disease, where 60 % of risk due to genetic factors, such as the Factor V Leiden (FVL) variant. DVT either asymptomatic or manifests with unspecific symptoms and, if left untreated, leads severe complications. The impact dramatic and currently, there still research gap in prevention. We characterized contribution stratified individuals based on makeup evaluate it favorably impacts prediction.MethodsIn UK Biobank (UKB), we performed...

The ABO gene contains three major alleles that encodes different antigens; A, B, and O, which determine an individual's blood group. Previous studies have primarily focused on identifying associations between groups diseases risk. Here, we sought to test for association genotypes (OO, OA, AA; OB, BB, AB) a large set of common inflammatory cardiovascular in UK Biobank as well disease-related protein biomarkers NSPHS. We first tested by conducting likelihood ratio test, testing whether...

Eosinophils play important roles in the release of cytokine mediators response to inflammation. Many associations between common genetic variants and eosinophils have already been reported, using single nucleotide polymorphism (SNP) array data. Here, we analyzed 200,000 whole-exome sequences (WES) from UK Biobank cohort performed gene-based analyses eosinophil count. We defined five different variant weighting schemes incorporate information on both deleteriousness frequency. A total 220...

Abstract Context Estradiol is the primary female sex hormone and plays an important role for skeletal health in both sexes. Several enzymes are involved estradiol metabolism but few genome-wide association studies (GWAS) have been performed to characterize genetic contribution variation estrogen levels. Objective Identify loci affecting levels estimate causal effect of on bone mineral density (BMD). Design We GWAS males (N = 147,690) females 163,985) from UK Biobank (UKB). was analyzed as a...

Background: Oral contraceptive use can influence the risk of many cancers and other diseases. However, so far, long-term effects oral contraceptives has not been extensively evaluated in relation to a broad set diseases disorders. In this observational study, we aimed clarify health related risks benefits associated with use. Methods: Women were classified as never or ever users, users further subdivided depending on duration Bonferroni correction for 26 common disease analysed applied....

ABSTRACT Background Deep Vein Thrombosis (DVT) is a common disease that can lead to serious complications such as pulmonary embolism and in-hospital mortality. More than 60% of DVT risk influenced by genetic factors, Factor V Leiden (FVL) prothrombin G20210A mutations (PTM). Characterising the contribution stratifying participants based on their makeup favourably impact prediction. Therefore, we aimed develop evaluate genetic-based prediction model for polygenic score (PRS) in UK Biobank...

Abstract Despite the success in identifying effects of common genetic variants, using genome-wide association studies (GWAS), much contribution to complex traits remains unexplained. Here, we analysed high coverage whole-genome sequencing (WGS) data, evaluate rare variants 414 plasma proteins. The frequency distribution was skewed towards spectrum, and damaging were more often rare. However, only 2.24% heritability estimated be explained by variants. A gene-based approach, developed also...

<div>Abstract<p>Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose this study is clarify time-dependent effects between long-term oral cancer risk. We performed an observational in 256,661 women from UK Biobank, born 1939 1970. Information on diagnoses were collected self-reported data national registers until March 2019. Cumulative over timespan study, as measured by OR, instantaneous risk, HR, assessed using...

<p>Online Data Supplements: • Online methods. Supplementary Table S1. A selection of previous studies aiming to estimate the effect oral contraceptive use on risk breast cancer. S2. Identification cancer cases in UK biobank database. S3. covariates database and their Odds ratio [OR] 95% confidence interval [CI]) odds S4. Fixed (time-independent) associations contraceptives, during after use, as analysed by Cox regression modelling. S5. contraceptives modelling with age primary time...

<p>Online Data Supplements: • Online methods. Supplementary Table S1. A selection of previous studies aiming to estimate the effect oral contraceptive use on risk breast cancer. S2. Identification cancer cases in UK biobank database. S3. covariates database and their Odds ratio [OR] 95% confidence interval [CI]) odds S4. Fixed (time-independent) associations contraceptives, during after use, as analysed by Cox regression modelling. S5. contraceptives modelling with age primary time...

<div>Abstract<p>Oral contraceptive use has been suggested to influence the risk of breast, ovarian, and endometrial cancer. The purpose this study is clarify time-dependent effects between long-term oral cancer risk. We performed an observational in 256,661 women from UK Biobank, born 1939 1970. Information on diagnoses were collected self-reported data national registers until March 2019. Cumulative over timespan study, as measured by OR, instantaneous risk, HR, assessed using...