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

Characterizing the ADHD phenotype for genetic studies

The genetic study of ADHD has made considerable progress. Further developments in the field will be reliant in part on identifying the most appropriate phenotypes for genetic analysis. The use of both categorical and dimensional measures of symptoms related to ADHD has been productive. The use of multiple reporters is a valuable feature of the characterization of psychopathology in children. It is argued that the use of aggregated measures to characterize the ADHD phenotype, particularly to establish its pervasiveness, is desirable. The recognition of the multiple comorbidities of ADHD can help to isolate more specific genetic influences. In relation to both reading disability and conduct disorder there is evidence that genes may be involved in the comorbid condition that are different from pure ADHD. To date, progress with the investigation of endophenotypes for ADHD has been disappointing. It is suggested that extending such studies beyond cognitive underpinnings to include physiological and metabolic markers might facilitate progress