A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk.

Pleiotropy, which consists of a single gene or allelic variant affecting multiple unrelated traits, is common across cancers, with evidence for genome-wide significant loci shared across cancer and noncancer traits. This feature is particularly relevant in multiple myeloma (MM) because several susceptibility loci that have been identified to date are pleiotropic. Therefore, the aim of this study was to identify novel pleiotropic variants involved in MM risk using 28 684 independent single nucleotide polymorphisms (SNPs) from GWAS Catalog that reached a significant association (P < 5 × 10 ) with their respective trait.

Does a Multiple Myeloma Polygenic Risk Score Predict Overall Survival of Patients with Myeloma?

Background: Genome-wide association studies (GWAS) of multiple myeloma in populations of European ancestry (EA) identified and confirmed 24 susceptibility loci. For other cancers (e.g.

Physicians' strategies for using family history data: having the data is not the same as using the data.

Objective: To identify needs in a clinical decision support tool development by exploring how primary care providers currently collect and use family health history (FHH).

Design: Survey questionnaires and semi-structured interviews were administered to a mix of primary and specialty care clinicians within the University of Utah Health system (40 surveys, 12 interviews).

Results: Three key themes emerged regarding providers' collection and use of FHH: (1) Strategies for collecting FHH vary by level of effort; (2) Documentation practices extend beyond the electronic health record's dedicated FHH module; and (3) Providers desire feedback from genetic services consultation and are uncertain how to refer patients to genetic services.

Genetic determinants of multiple myeloma risk within the Wnt/beta-catenin signaling pathway.

Background: Aberrant Wnt/beta-catenin pathway activation is implicated in Multiple Myeloma (MM) development, but little is known if genetic variants within this pathway contribute to MM susceptibility.

Methods: We performed a discovery candidate pathway analysis in 269 non-Hispanic white MM cases and 272 controls focusing on 171 variants selected from 26 core genes within the Wnt/beta-catenin pathway. Significant candidate variants (P < 0.

Expression quantitative trait loci of genes predicting outcome are associated with survival of multiple myeloma patients.

Gene expression profiling can be used for predicting survival in multiple myeloma (MM) and identifying patients who will benefit from particular types of therapy. Some germline single nucleotide polymorphisms (SNPs) act as expression quantitative trait loci (eQTLs) showing strong associations with gene expression levels. We performed an association study to test whether eQTLs of genes reported to be associated with prognosis of MM patients are directly associated with measures of adverse outcome.

Coinherited genetics of multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance.

So far, 23 germline susceptibility loci have been associated with multiple myeloma (MM) risk. It is unclear whether the genetic variation associated with MM susceptibility also predisposes to its precursor, monoclonal gammopathy of undetermined significance (MGUS). Leveraging 2434 MM cases, 754 MGUS cases, and 2 independent sets of controls (2567/879), we investigated potential shared genetic susceptibility of MM and MGUS by (1) performing MM and MGUS genome-wide association studies (GWAS); (2) validating the association of a polygenic risk score (PRS) based on 23 established MM loci (MM-PRS) with risk of MM, and for the first time with MGUS; and (3) examining genetic correlation of MM and MGUS.

Critical care information display approaches and design frameworks: A systematic review and meta-analysis.

Objective: To systematically review original user evaluations of patient information displays relevant to critical care and understand the impact of design frameworks and information presentation approaches on decision-making, efficiency, workload, and preferences of clinicians.

Methods: We included studies that evaluated information displays designed to support real-time care decisions in critical care or anesthesiology using simulated tasks. We searched PubMed and IEEExplore from 1/1/1990 to 6/30/2018.

Novel displays of patient information in critical care settings: a systematic review.

Objective: Clinician information overload is prevalent in critical care settings. Improved visualization of patient information may help clinicians cope with information overload, increase efficiency, and improve quality. We compared the effect of information display interventions with usual care on patient care outcomes.

Critical care information display approaches and design frameworks: A systematic review and meta-analysis.

Objective: To systematically review original user evaluations of patient information displays relevant to critical care and understand the impact of design frameworks and information presentation approaches on decision-making, efficiency, workload, and preferences of clinicians.

Methods: We included studies that evaluated information displays designed to support real-time care decisions in critical care or anesthesiology using simulated tasks. We searched PubMed and IEEExplore from 1/1/1990 to 6/30/2018.

Patient information organization in the intensive care setting: expert knowledge elicitation with card sorting methods.

Introduction: Many electronic health records fail to support information uptake because they impose low-level information organization tasks on users. Clinical concept-oriented views have shown information processing improvements, but the specifics of this organization for critical care are unclear.

Objective: To determine high-level cognitive processes and patient information organization schema in critical care.

Germline Lysine-Specific Demethylase 1 () Mutations Confer Susceptibility to Multiple Myeloma.

Given the frequent and largely incurable occurrence of multiple myeloma, identification of germline genetic mutations that predispose cells to multiple myeloma may provide insight into disease etiology and the developmental mechanisms of its cell of origin, the plasma cell (PC). Here, we identified familial and early-onset multiple myeloma kindreds with truncating mutations in lysine-specific demethylase 1 (LSD1/KDM1A), an epigenetic transcriptional repressor that primarily demethylates histone H3 on lysine 4 and regulates hematopoietic stem cell self-renewal. In addition, we found higher rates of germline truncating and predicted deleterious missense KDM1A mutations in patients with multiple myeloma unselected for family history compared with controls.

Discordant Haplotype Sequencing Identifies Functional Variants at the 2q33 Breast Cancer Risk Locus.

The findings from genome-wide association studies hold enormous potential for novel insight into disease mechanisms. A major challenge in the field is to map these low-risk association signals to their underlying functional sequence variants (FSV). Simple sequence study designs are insufficient, as the vast numbers of statistically comparable variants and a limited knowledge of noncoding regulatory elements complicate prioritization.