To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1 . In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P <5×10 −8 , bringing the number of known independent signals for CRC to approximately 100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs, somatic drivers, and support a role of immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of underlying biology, and impact personalized screening strategies and drug development.

This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.

Purpose: The aim of this study was to assess different aspects of reliability in high resolution ultrasonography (HRUS) of the peripheral nerves and to establish reference values for the most frequently examined nerve segments. Materials and Methods:A nerve size parameter, the cross-sectional area (CSA) of the C5, C6 and C7 cervical roots, the median, ulnar, radial, superficial radial, peroneal, tibial, and the sural nerves was measured using HRUS at altogether 14 predefined anatomical sites in two different cohorts of healthy subjects (n=56), and the inter-rater, intra-rater and interequipment reliability of measurements was assessed.Results: Mean CSA of the 14 nerve segments ranged from 2 to 10 mm 2 . Intra-rater, inter-rater and inter-equipment reliability was high with intraclass correlation coefficients of 0.93, 0.98, and 0.86, respectively. CSA values showed no consistent correlation with age, height, and body weight, but males had significantly larger values than females for nerve segments on the arm after correcting for age, weight and height in multivariate analysis. CSA values did not differ when two independent cohorts were compared. Conclusion:Peripheral nerve ultrasonography is a reliable and reproducible diagnostic method in the hands of experienced examiners. Normal values for several upper and lower extremity nerves are provided by our study.

on behalf of the German-Dutch Ross Registry Background-Autograft reinforcement interventions (R) during the Ross procedure are intended to preserve autograft function and improve durability. The aim of this study is to evaluate this hypothesis. Methods and Results-1335 adult patients (mean age:43.5Ϯ12.0 years) underwent a Ross procedure (subcoronary, SC, nϭ637; root replacement, Root, nϭ698). 592 patients received R of the annulus, sinotubular junction, or both. Regular clinical and echocardiographic follow-up was performed (mean:6.09Ϯ3.97, range:0.01 to 19.2 years). Longitudinal assessment of autograft function with time was performed using multilevel modeling techniques. The Root without R (RootϪR) group was associated with a 6ϫ increased reoperation rate compared to Root with R (RootϩR), SC with R (SCϩR), and without R (SC-R; 12.9% versus 2.3% versus 2.5%.versus 2.6%, respectively; PϽ0.001). SC and Root groups had similar rate of aortic regurgitation (AR) development over time. RootϩR patients had no progression of AR, whereas RootϪR had 6 times higher AR development compared to RootϩR. In SC, R had no remarkable effect on the annual AR progression. The SC technique was associated with lower rates of autograft dilatation at all levels of the aortic root compared to the Root techniques. R did not influence autograft dilatation rates in the Root group. Conclusions-For the time period of the study surgical autograft stabilization techniques preserve autograft function and result in significantly lower reoperation rates. The nonreinforced Root was associated with significant adverse outcome. Therefore, surgical stabilization of the autograft is advisable to preserve long-term autograft function, especially in the Root Ross procedure. (Circulation. 2009;120[suppl 1]:S146-S154.)