Genome sequencing in the clinic: the past, present, and future of genomic medicine.

Genomic sequencing has undergone massive expansion in the past 10 yr, from a rarely used research tool into an approach that has broad applications in a clinical setting. From rare disease to cancer, genomics is transforming our knowledge of biology. The transition from targeted gene sequencing, to whole exome sequencing, to whole genome sequencing has only been made possible due to rapid advancements in technologies and informatics that have plummeted the cost per base of DNA sequencing and analysis. The tools of genomics have resolved the etiology of disease for previously undiagnosable conditions, identified cancer driver gene variants, and have impacted the understanding of pathophysiology for many diseases. However, this expansion of use has also highlighted research's current voids in knowledge. The lack of precise animal models for gene-to-function association, lack of tools for analysis of genomic structural changes, skew in populations used for genetic studies, publication biases, and the "Unknown Proteome" all contribute to voids needing filled for genomics to work in a fast-paced clinical setting. The future will hold the tools to fill in these voids, with new data sets and the continual development of new technologies allowing for expansion of genomic medicine, ushering in the days to come for precision medicine. In this review we highlight these and other points in hopes of advancing and guiding precision medicine into the future for optimal success.

Attitudes towards childbearing, causal attributions for bipolar disorder and psychological distress: a study of families with multiple cases of bipolar disorder.

BACKGROUND: For families with multiple cases of bipolar disorder this study explored: attitudes towards childbearing; causal attributions for bipolar disorder, in particular the degree to which a genetic model is endorsed and its impact on the perceived stigma of bipolar disorder; and predictors of psychological distress. METHOD: Two hundred individuals (95 unaffected and 105 affected with either bipolar disorder, schizo-affective disorder - manic type, or recurrent major disorder) were surveyed, using mailed, self-administered questionnaires. RESULTS: Thirty-five (35%) participants reported being 'not at all willing to have children' or 'less willing to have children' as a result of having a strong family history of bipolar disorder. Being not at all or less willing to have children was associated with perceived stigma of bipolar disorder [odds ratio (OR) 2.42, p = 0.002], endorsement of a genetic model (OR 1.76, p = 0.046), and being affected (OR 2.16, p = 0.01). Among unaffected participants only, endorsement of a genetic model was strongly correlated with perceived stigma (rs = 0.30, p = 0.004). Perceiving the family environment as an important factor in causing bipolar disorder was significantly associated with psychological distress (OR 1.58, p = 0.043) among unaffected participants. Among affected participants, perceived stigma was significantly correlated with psychological distress (OR 2.44, p = 0.02), controlling for severity of symptoms (p < 0.001). CONCLUSIONS: Having a genetic explanation for bipolar disorder may exacerbate associative stigma among unaffected members from families with multiple cases of bipolar disorder, while it does not impact on perceived stigma among affected family members. Affected family members may benefit from interventions to ameliorate the adverse effects of perceived stigma.