Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

The criminal profiling illusion:what's behind the smoke and mirrors?

There is a belief that criminal profilers can predict a criminal's characteristics from crime scene evidence. In this article, the authors argue that this belief may be an illusion and explain how people may have been misled into believing that criminal profiling (CP) works despite no sound theoretical grounding and no strong empirical support for this possibility. Potentially responsible for this illusory belief is the information that people acquire about CP, which is heavily influenced by anecdotes, repetition of the message that profiling works, the expert profiler label, and a disproportionate emphasis on correct predictions. Also potentially responsible are aspects of information processing such as reasoning errors, creating meaning out of ambiguous information, imitating good ideas, and inferring fact from fiction. The authors conclude that CP should not be used as an investigative tool because it lacks scientific support