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Refining breast cancer genetic risk and biology through multi-ancestry fine-mapping analyses of 192 risk regions.

Nat Genet

January 2025

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.

Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.

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Objectives: The 2022 US Supreme Court decision dramatically shifted the legal landscape in health care, leaving state legislatures to redefine the ethics of medical practice. As gold-standard medical procedures become banned and criminalized, physicians are facing heightened legal uncertainty and grappling with moral dilemmas of where and how to practice. This study aimed to quantitatively assess trends in legal concern among medical students and identify correlations with decision making regarding future medical training.

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Background: Several viruses have been linked to Alzheimer disease (AD) by independent lines of evidence.

Method: Whole genome and whole exome sequences (WGS/WES) derived from brain (3,404 AD cases, 894 controls) and blood (15,612 AD cases, 24,544 controls) obtained from European ancestry (EU), African American (AA), Mexican (HMX), South Asian Indian (IND), and Caribbean Hispanic (CH) participants of the Alzheimer's Disease Sequencing Project (ADSP) and 276 AD cases 3,584 controls (all EU) from the Framingham Heart Study (FHS) that did not align to the human reference genome were aligned to viral reference genomes. A genome-wide association study (GWAS) for viral DNA load was conducted using PLINK software and regression models with covariates for sex, age, ancestry principal components, and tissue source.

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Background: With a rapidly aging population, South Korea anticipates a surge in Alzheimer disease (AD). However, the genetic basis of AD in Koreans is not well understood.

Method: We sequenced the genomes of 3,540 Koreans (1,583 AD cases and 1,957 controls) older than age 60 and performed a genome-wide association study (GWAS) of AD using logistic regression models that included covariates for age, sex, five ancestry principal components, and an empirical genetic relationship matrix.

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