Shared heritability and functional enrichment across six solid cancers

Correction: Nature Communications 10 (2019): art. 4386 DOI: 10.1038/s41467-019-12095-8Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.Peer reviewe

Shared heritability and functional enrichment across six solid cancers

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis

Advancing the science of patient safety and quality improvement to the next level

This paper describes our journey to advance the science and practice of patient safety and quality improvement. The journey began with efforts to identify hazards through an incident reporting system called the Intensive Care Unit Safety Reporting System. We quickly found that identifying hazards was merely a first step. We also needed to investigate and learn from these hazards to prevent patient harm. Therefore, we developed the Comprehensive Unit-based Safety Program (CUSP) to identify and learn from local defects and improve teamwork and safety culture. Teams across many units faced common problems, such as healthcare-acquired infections, for which there is empiric evidence on prevention practices, but the evidence is unreliably applied. This discovery led us to develop a model to translate research into practice (TRIP). We combined TRIP with CUSP for the Keystone ICU Project design, with the goal of improving care for adult patients in Michigan intensive care units (ICUs). The resulting dramatic and sustained reductions in central line-associated bloodstream infections (CLABSIs) in Michigan led to a national initiative to reduce CLABSIs across the United States. Applying the perspectives from different academic disciplines helped us learn how this national effort succeeded, an approach we also used to study cardiac surgery-related errors. Still, the CLABSI effort addressed one type of harm, while patients are at risk for over a dozen and care systems relying more on the heroism of clinicians than on safe design. Current efforts include building a quality management infrastructure to support improvement work and defining the skills, resources, and accountability needed at every level of a health system. We are also partnering with patients, their loved ones, and others to eliminate all harms, optimize patient experience and outcomes, and reduce waste. In this trans-disciplinary systems approach, we hope to reduce all harms, improve productivity, and enhance joy for clinicians