Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

Background and aimsThe associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis).DesignPolygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families.SettingSix sites in the United States.ParticipantsEuropean ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample.MeasurementsOutcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment.FindingsIn polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R2 ) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R2 0.13-0.20%).ConclusionsIndividuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education)

Exploring patterns of recurrent melanoma in Northeast Scotland to inform the introduction a digital self-examination intervention

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Deep and Comparative Transcriptome Analysis of Rice Plants Infested by the Beet Armyworm (\u3ci\u3eSpodoptera exigua\u3c/i\u3e) and Water Weevil (\u3ci\u3eLissorhoptrus oryzophilus\u3c/i\u3e)

The beet armyworm (Spodoptera exigua) and the rice water weevil (Lissorhoptrus oryzophilus) are two important insect pests in rice production. To identify insect-responsive genes in rice, we performed a deep transcriptome analysis of Nipponbare rice leaves infested with both beet armyworm and water weevil using massively parallel signature sequencing (MPSS). Many antisense, alternative, and novel transcripts were commonly and specifically induced and suppressed in the infested tissue. Key genes involved in the defense metabolic pathways such as salicylic acid and jasmonic acid biosynthesis pathways were up-regulated in the infested leaves. To validate theMPSS results, we analyzed the transcriptome of the rice leaves infested with water weevils using Solexa’s sequencing-bysynthesis (SBS) method. The MPSS and SBS data were highly correlated (Pearson’s correlation coefficient=0.85), and 83% of genes had similar gene expression in both libraries. Our comprehensive and in-depth survey of the insect-infested libraries provides a rich genomic resource for further analyzing the function of key regulatory genes involved in insect resistance in rice. Supplementary files are attached below

Gambling Warning Messages: The Impact of Winning and Losing on Message Reception across a Gambling Episode

Warning messages prevent and modify risk-taking behaviors. When controlling the outcome of each wager, studies suggest such messages can increase a player’s knowledge about gambling-specific risks, modify their gambling-related cognitive distortions, and even change play. The present study takes the next step by asking if the reception of the warning message is influenced by the player’s experience of winning or losing. In a laboratory study, participants were randomly assigned to a winning or losing gambling experience where they either viewed periodic warning messages or not. Using a mixed model analysis, the influence of the warning messages was related to players’ winning or losing over the course of the wagering session. Those in the warning message-win condition made the fewest number of spins, F(3,144) = 3.1, p \u3c .05, and did not increase their betting rate over the course of play compared to the losing or no message conditions. Those in the warning message-loss condition decreased the size of their bets over the course of play compared to those who received messages while winning, t(24671) = -7.9, p \u3c .05. Whether an individual is winning or losing may have significant consequences on the impact of a warning message. Whereas a message to change gambling behavior may be able to encourage a winning gambler to stop play, the same message for a losing player may lead to a small minimization in harm by helping them to decrease their bet size

HSD3B1 genotype identifies glucocorticoid responsiveness in severe asthma

Asthma resistance to glucocorticoid treatment is a major health problem with unclear etiology. Glucocorticoids inhibit adrenal androgen production. However, androgens have potential benefits in asthma. HSD3B1 encodes for 3β-hydroxysteroid dehydrogenase-1 (3β-HSD1), which catalyzes peripheral conversion from adrenal dehydroepiandrosterone (DHEA) to potent androgens and has a germline missense-encoding polymorphism. The adrenal restrictive HSD3B1(1245A) allele limits conversion, whereas the adrenal permissive HSD3B1(1245C) allele increases DHEA metabolism to potent androgens. In the Severe Asthma Research Program (SARP) III cohort, we determined the association between DHEA-sulfate and percentage predicted forced expiratory volume in 1 s (FEV1PP). HSD3B1(1245) genotypes were assessed, and association between adrenal restrictive and adrenal permissive alleles and FEV1PP in patients with (GC) and without (noGC) daily oral glucocorticoid treatment was determined (n = 318). Validation was performed in a second cohort (SARP I&II; n = 184). DHEA-sulfate is associated with FEV1PP and is suppressed with GC treatment. GC patients homozygous for the adrenal restrictive genotype have lower FEV1PP compared with noGC patients (54.3% vs. 75.1%; P < 0.001). In patients with the homozygous adrenal permissive genotype, there was no FEV1PP difference in GC vs. noGC patients (73.4% vs. 78.9%; P = 0.39). Results were independently confirmed: FEV1PP for homozygous adrenal restrictive genotype in GC vs. noGC is 49.8 vs. 63.4 (P < 0.001), and for homozygous adrenal permissive genotype, it is 66.7 vs. 67.7 (P = 0.92). The adrenal restrictive HSD3B1(1245) genotype is associated with GC resistance. This effect appears to be driven by GC suppression of 3β-HSD1 substrate. Our results suggest opportunities for prediction of GC resistance and pharmacologic intervention

Joint Statement on Pediatric Education at Schools of Pharmacy

Providing health care for children is a unique specialty, and pediatric patients represent approximately 25% of the population. Education of pharmacy students on patients across the lifespan is required by current Accreditation Council for Pharmacy Education standards and outcomes; thus, it is essential that pharmacy students gain a proficiency in caring for children. A collaborative panel of pediatric faculty members from schools and colleges of pharmacy was established to review the current literature regarding pediatric education in Doctor of Pharmacy curricula and establish updated recommendations for the provision of pediatric pharmacy education. This statement outlines five recommendations supporting inclusion of pediatric content and skills in Doctor of Pharmacy curricula

Using polygenic scores for identifying individuals at increased risk of substance use disorders in clinical and population samples

Genome-wide, polygenic risk scores (PRS) have emerged as a useful way to characterize genetic liability. There is growing evidence that PRS may prove useful for early identification of those at increased risk for certain diseases. The current potential of PRS for alcohol use disorders (AUD) remains an open question. Using data from both a population-based sample [the FinnTwin12 (FT12) study] and a high-risk sample [the Collaborative Study on the Genetics of Alcoholism (COGA)], we examined the association between PRSs derived from genome-wide association studies (GWASs) of (1) alcohol dependence/alcohol problems, (2) alcohol consumption, and (3) risky behaviors with AUD and other substance use disorder (SUD) criteria. These PRSs explain similar to 2.5-3.5% of the variance in AUD (across FT12 and COGA) when all PRSs are included in the same model. Calculations of area under the curve (AUC) show PRS provide only a slight improvement over a model with age, sex, and ancestral principal components as covariates. While individuals in the top 20, 10, and 5% of the PRS distribution had greater odds of having an AUD compared to the lower end of the continuum in both COGA and FT12, the point estimates at each threshold were statistically indistinguishable. Those in the top 5% reported greater levels of licit (alcohol and nicotine) and illicit (cannabis and opioid) SUD criteria. PRSs are associated with risk for SUD in independent samples. However, usefulness for identifying those at increased risk in their current form is modest, at best. Improvement in predictive ability will likely be dependent on increasing the size of well-phenotyped discovery samples.Peer reviewe

Clusters of Galaxies in the First Half of the Universe from the IRAC Shallow Survey

We have identified 335 galaxy cluster and group candidates, 106 of which are at z > 1, using a 4.5 um selected sample of objects from a 7.25 deg^2 region in the Spitzer Infrared Array Camera (IRAC) Shallow Survey. Clusters were identified as 3-dimensional overdensities using a wavelet algorithm, based on photometric redshift probability distributions derived from IRAC and NOAO Deep Wide-Field Survey data. We estimate only ~10% of the detections are spurious. To date 12 of the z > 1 candidates have been confirmed spectroscopically, at redshifts from 1.06 to 1.41. Velocity dispersions of ~750 km/s for two of these argue for total cluster masses well above 10^14 M_sun, as does the mass estimated from the rest frame near infrared stellar luminosity. Although not selected to contain a red sequence, some evidence for red sequences is present in the spectroscopically confirmed clusters, and brighter galaxies are systematically redder than the mean galaxy color in clusters at all redshifts. The mean I - [3.6] color for cluster galaxies up to z ~ 1 is well matched by a passively evolving model in which stars are formed in a 0.1 Gyr burst starting at redshift z_f = 3. At z > 1, a wider range of formation histories is needed, but higher formation redshifts (i.e. z_f > 3) are favored for most clusters.Comment: 56 pages, 19 figures, 3 tables, landscape tables 1 (p. 14) and 2 (p. 29) should be printed separately. Accepted for publication in Astrophysical Journal, updated version will be posted upon publicatio