Further evidence for a relatively high sea level during the penultimate interglacial: open-system U-series ages from La Marina (Alicante, East Spain)

The elevation and timing of high sea stands during Oxygen Isotope Stage (OIS) 7 are not as well constraíned as those of OIS 5e. Conflictíng values are reported from Medíterranean coastlines, and fossil dating is inaccurate because of ubiquitous open U-series systems. New morphostratigraphic data from La Marina (eastem Spain) supported by open-system U-series coral ages shed light on the maximum sea level duríng OIS 7. Fossil corals (Cladocora Caespitosa) underlying an OIS 5e marine unít yielded U-series ages from 178 ± (0 to 208 ± 1) ka (± 20σ n=7) with an outlier al 240 ± 18 ka. Mean open-system limit ages of 170 ± 10 (minimum age after correction for 234Th-230Th uptake) and 237 ± 20 ka (maximum ase after correction for 238U - 234U uptake) were calculated to have a probable age closer to the minimum value, for an assignment of OlS 7a or 7c. The occurrence of a warn-water "Senegalese" fauna (Strombus bubonius) in OIS5e and OIS 7 marine units confirms the arrival of tropical species to the Mediterranean before the last interglacial periodo Morpho-sedimentological and neotectonic studies suggest that the maximum paleo-sea level during OIS 7c or 7a was a few melers below that of OlS Se

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice