Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV.

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues.

Adherence with direct oral anticoagulants in patients with atrial fibrillation: Trends, risk factors, and outcomes.

Background: Adherence to direct oral anticoagulants (DOACs) remains a concern among non-valvular atrial fibrillation (AF) patients. We aimed to assess patterns of adherence with DOACs and examine their association with ischemic stroke and systemic embolism (SE).

Methods: This retrospective cohort study includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed non-valvular AF between January 2014 and March 2019, who initiated DOACs within 90 days of AF diagnosis and used DOACs exclusively.

Implementation of oral anticoagulation treatment guidelines in patients with newly diagnosed atrial fibrillation.

Aims: Oral anticoagulants (OACs) are considered the mainstay in preventing stroke in atrial fibrillation (AF). OAC treatment remains suboptimal among AF patients, even after the introduction of direct oral anticoagulants (DOACs). We aimed to assess trends overtime and current implementation of OAC treatment guidelines in AF, using a large dataset of real world data from Israel.

Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors.