Longitudinal associations between incident lumbar spine MRI findings and chronic low back pain or radicular symptoms: retrospective analysis of data from the longitudinal assessment of imaging and disability of the back (LAIDBACK)

BACKGROUND: There are few longitudinal cohort studies examining associations between incident MRI findings and incident spine-related symptom outcomes. Prior studies do not discriminate between the two distinct outcomes of low back pain (LBP) and radicular symptoms. To address this gap in the literature, we conducted a secondary analysis of existing data from the Longitudinal Assessment of Imaging and Disability of the Back (LAIDBACK). The purpose of this study was to examine the association of incident lumbar MRI findings with two specific spine-related symptom outcomes: 1) incident chronic bothersome LBP, and 2) incident radicular symptoms such as pain, weakness, or sensation alterations in the lower extremity. METHODS: The original LAIDBACK study followed 123 participants without current LBP or sciatica, administering standardized MRI assessments of the lumbar spine at baseline and at 3-year follow-up, and collecting information on participant-reported spine-related symptoms and signs every 4 months for 3 years. These analyses examined bivariable and multivariable associations between incident MRI findings and symptom outcomes (LBP and radicular symptoms) using logistic regression. RESULTS: Three-year cumulative incidence of new MRI findings ranged between 2 and 8%, depending on the finding. Incident annular fissures were associated with incident chronic LBP, after adjustment for prior back pain and depression (adjusted odds ratio [OR] 6.6; 95% confidence interval [CI] 1.2-36.9). All participants with incident disc extrusions (OR 5.4) and nerve root impingement (OR 4.1) reported incident radicular symptoms, although associations were not statistically significant. No other incident MRI findings showed large magnitude associations with symptoms. CONCLUSIONS: Even when applying more specific definitions for spine-related symptom outcomes, few MRI findings showed large magnitude associations with symptom outcomes. Although incident annular fissures, disc extrusions, and nerve root impingement were associated with incident symptom outcomes, the 3-year incidence of these MRI findings was extremely low, and did not explain the vast majority of incident symptom cases

Genetic variation in the SIM1 locus is associated with erectile dysfunction.

Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10-25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10-14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function

Copy number variation analysis in the context of electronic medical records and large-scale genomics consortium efforts

The goal of this paper is to review recent research on copy number variations (CNVs) and their association with complex and rare diseases. In the latter part of this paper, we focus on how large biorepositories such as the electronic medical record and genomics (eMERGE) consortium may be best leveraged to systematically mine for potentially pathogenic CNVs, and we end with a discussion of how such variants might be reported back for inclusion in electronic medical records as part of medical history

Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNPs) affecting high density lipoprotein (HDL) or low density lipoprotein (LDL) cholesterol levels; these SNPs may contribute to the genetic basis of vascular diseases.</p> <p>Results</p> <p>We assessed the impact of 34 SNPs at 23 loci on dyslipidemia, key lipid sub-phenotypes, and severe carotid artery disease (CAAD) in a case-control cohort. The effects of these SNPs on HDL and LDL were consistent with those previously reported, and we provide unbiased estimates of the percent variance in HDL (3.9%) and LDL (3.3%) explained by genetic risk scores. We assessed the effects of these SNPs on HDL subfractions, apolipoprotein A-1, LDL buoyancy, apolipoprotein B, and lipoprotein (a) and found that rs646776 predicts apolipoprotein B level while rs2075650 predicts LDL buoyancy. Finally, we tested the role of these SNPs in conferring risk for ultrasonographically documented CAAD stenosis status. We found that two loci, chromosome 1p13.3 near CELSR2 and PSRC1 which contains rs646776, and 19q13.2 near TOMM40 and APOE which contains rs2075650, harbor risk alleles for CAAD.</p> <p>Conclusion</p> <p>Our analysis of 34 SNPs contributing to dyslipidemia at 23 loci suggests that genetic variation in the 1p13.3 region may increase risk of CAAD by increasing LDL particle number, whereas variation in the 19q13.2 region may increase CAAD risk by promoting formation of smaller, denser LDL particles.</p

Patients' Choices for Return of Exome Sequencing Results to Relatives in the Event of Their Death

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/116009/1/jlme12290.pd

Sequential effects in two-choice reaction time tasks: decomposition and synthesis of mechanisms

Performance on serial tasks is influenced by first- and higher-order sequential effects, respectively due to the immediately previous and earlier trials. As response-to-stimulus interval (RSI) increases, the pattern of reaction times transits from a benefit-only mode, traditionally ascribed to automatic facilitation (AF), to a cost-benefit mode, due to strategic expectancy (SE). To illuminate the sources of such effects, we develop a connectionist network of two mutually-inhibiting neural decision units subject to feedback from previous trials. A study of separate biasing mechanisms shows that residual decision unit activity can lead only to first-order AF, but higher-order AF can result from strategic priming mediated by conflict-monitoring, which we instantiate in two distinct versions. A further mechanism mediates expectation-related biases that grow during RSI toward saturation levels determined by weighted repetition (or alternation) sequence lengths. Equipped with these mechanisms, the network, consistent with known neurophysiology, accounts for several sets of behavioral data over a wide range of RSIs. The results also suggest that practice speeds up all the mechanisms rather than adjusting their relative strengths