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. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history), and on average 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

This is a pre-copyedited, author-produced version of an article accepted for publication in Nature Genetics following peer review. The version of record "Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries"

In the version of this article initially published, the author affiliations incorrectly listed "Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy" as "Candiolo Cancer Institute, Candiolo, Italy." The change has been made to the HTML and PDF versions of the article.

This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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.Methods: This is a retrospective cohort study that includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed nonvalvular AF between January 2014 and December 2019 with CHA 2 DS 2 -VASc score ≥2. OAC treatment rates were calculated and multivariate regression models were used to identify predictors of OACs initiation.Results: Overall, 46 531 patients were included in the study. The 3-months cumulative OAC treatment rates increased consistently over the years: 46.9% (95% confi-