Prescription opioid use disorder and heroin use among 12-34 year-olds in the United States from 2002 to 2014

Trend analyses of prescription opioids in the U.S. indicate use, especially use of prescription opioids stronger than morphine, has more than doubled among adults since the early 1990's (Frenk, Porter, & Paulozzi, 2015). Prescription opioids, like Oxycontin®, are effective pharmacological treatments for acute and chronic pain (Fitzcharles and Shir, 2009 ; Gallagher and Rosenthal, 2008). When used as indicated, these medications can be an important component of pain management. However, their high abuse potential presents concerns regarding their nonmedical use, which can be defined as ‘use of a prescription opioid that was not prescribed, or taken for the experience or feeling it caused’ (SAMHSA, 2014). In the United States, nonmedical use of prescription opioids (NMPO) is increasingly recognized as a serious public health problem among adults (Blanco et al., 2007; Han et al., 2015 ; Huang et al., 2006). Nonmedical prescription drug use, specifically nonmedical use of prescription opioids, is also a growing problem in other countries such as Canada (Fischer et al., 2014 ; Fischer et al., 2013) and Australia (Degenhardt et al., 2006 ; Rintoul et al., 2011)

Systematic Inference of Copy-Number Genotypes from Personal Genome Sequencing Data Reveals Extensive Olfactory Receptor Gene Content Diversity

Copy-number variations (CNVs) are widespread in the human genome, but comprehensive assignments of integer locus copy-numbers (i.e., copy-number genotypes) that, for example, enable discrimination of homozygous from heterozygous CNVs, have remained challenging. Here we present CopySeq, a novel computational approach with an underlying statistical framework that analyzes the depth-of-coverage of high-throughput DNA sequencing reads, and can incorporate paired-end and breakpoint junction analysis based CNV-analysis approaches, to infer locus copy-number genotypes. We benchmarked CopySeq by genotyping 500 chromosome 1 CNV regions in 150 personal genomes sequenced at low-coverage. The assessed copy-number genotypes were highly concordant with our performed qPCR experiments (Pearson correlation coefficient 0.94), and with the published results of two microarray platforms (95–99% concordance). We further demonstrated the utility of CopySeq for analyzing gene regions enriched for segmental duplications by comprehensively inferring copy-number genotypes in the CNV-enriched >800 olfactory receptor (OR) human gene and pseudogene loci. CopySeq revealed that OR loci display an extensive range of locus copy-numbers across individuals, with zero to two copies in some OR loci, and two to nine copies in others. Among genetic variants affecting OR loci we identified deleterious variants including CNVs and SNPs affecting ∼15% and ∼20% of the human OR gene repertoire, respectively, implying that genetic variants with a possible impact on smell perception are widespread. Finally, we found that for several OR loci the reference genome appears to represent a minor-frequency variant, implying a necessary revision of the OR repertoire for future functional studies. CopySeq can ascertain genomic structural variation in specific gene families as well as at a genome-wide scale, where it may enable the quantitative evaluation of CNVs in genome-wide association studies involving high-throughput sequencing

High-Resolution Copy-Number Variation Map Reflects Human Olfactory Receptor Diversity and Evolution

Olfactory receptors (ORs), which are involved in odorant recognition, form the largest mammalian protein superfamily. The genomic content of OR genes is considerably reduced in humans, as reflected by the relatively small repertoire size and the high fraction (∼55%) of human pseudogenes. Since several recent low-resolution surveys suggested that OR genomic loci are frequently affected by copy-number variants (CNVs), we hypothesized that CNVs may play an important role in the evolution of the human olfactory repertoire. We used high-resolution oligonucleotide tiling microarrays to detect CNVs across 851 OR gene and pseudogene loci. Examining genomic DNA from 25 individuals with ancestry from three populations, we identified 93 OR gene loci and 151 pseudogene loci affected by CNVs, generating a mosaic of OR dosages across persons. Our data suggest that ∼50% of the CNVs involve more than one OR, with the largest CNV spanning 11 loci. In contrast to earlier reports, we observe that CNVs are more frequent among OR pseudogenes than among intact genes, presumably due to both selective constraints and CNV formation biases. Furthermore, our results show an enrichment of CNVs among ORs with a close human paralog or lacking a one-to-one ortholog in chimpanzee. Interestingly, among the latter we observed an enrichment in CNV losses over gains, a finding potentially related to the known diminution of the human OR repertoire. Quantitative PCR experiments performed for 122 sampled ORs agreed well with the microarray results and uncovered 23 additional CNVs. Importantly, these experiments allowed us to uncover nine common deletion alleles that affect 15 OR genes and five pseudogenes. Comparison to the chimpanzee reference genome revealed that all of the deletion alleles are human derived, therefore indicating a profound effect of human-specific deletions on the individual OR gene content. Furthermore, these deletion alleles may be used in future genetic association studies of olfactory inter-individual differences

Exposure to Terrorism and Israeli Youths’ Cigarette, Alcohol, and Cannabis Use

Objectives. We investigated the consequences of exposure to acts of terrorism among Israeli adolescents. We examined whether exposure to terrorism predicted adolescents’ use of cigarettes, alcohol (including binge drinking), and cannabis after we controlled for posttraumatic stress and depressive symptoms and background variables