Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Focus on poleward shifts in species' distribution underestimates the fingerprint of climate change

Species are largely predicted to shift poleward as global temperatures increase, with this fingerprint of climate change being already observed across a range of taxonomic groups and, mostly temperate, geographic locations¹⁻⁵. However, the assumption of uni-directional distribution shifts does not account for complex interactions among temperature, precipitation and species-specific tolerances⁶, all of which shape the direction and magnitude of changes in a species' climatic niche. We analysed 60 years of past climate change on the Australian continent, assessing the velocity of changes in temperature and precipitation, as well as changes in climatic niche space for 464 Australian birds. We show large magnitude and rapid rates of change in Australian climate over the past 60 years resulting in high-velocity and multi-directional, including equatorial, shifts in suitable climatic space for birds (ranging from 0.1 to 7.6 km yr⁻¹, mean 1.27 km yr⁻¹). Overall, if measured only in terms of poleward distribution shifts, the fingerprint of climate change is underestimated by an average of 26% in temperate regions of the continent and by an average of 95% in tropical regions. We suggest that the velocity of movement required by Australian species to track their climatic niche may be much faster than previously thought and that the interaction between temperature and precipitation changes will result in multi-directional distribution shifts globally