Genome-wide analysis of self-reported risk-taking behaviour and cross-disorder genetic correlations in the UK Biobank cohort.

Risk-taking behaviour is a key component of several psychiatric disorders and could influence lifestyle choices such as smoking, alcohol use, and diet. As a phenotype, risk-taking behaviour therefore fits within a Research Domain Criteria (RDoC) approach, whereby identifying genetic determinants of this trait has the potential to improve our understanding across different psychiatric disorders. Here we report a genome-wide association study in 116,255 UK Biobank participants who responded yes/no to the question "Would you consider yourself a risk taker?" Risk takers (compared with controls) were more likely to be men, smokers, and have a history of psychiatric disorder.

Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia.

Background: There are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity.

Methods: We tested the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schizophrenia and substance use disorder. To do this, polygenic risk scores for schizophrenia derived from a large meta-analysis by the Psychiatric Genomics Consortium were computed in three substance use disorder datasets: the Collaborative Genetic Study of Nicotine Dependence (ascertained for tobacco use disorder; n = 918 cases; 988 control subjects), the Collaborative Study on the Genetics of Alcoholism (ascertained for alcohol use disorder; n = 643 cases; 384 control subjects), and the Family Study of Cocaine Dependence (ascertained for cocaine use disorder; n = 210 cases; 317 control subjects).

Genetic correlation between smoking behaviors and schizophrenia.

Nicotine dependence is highly comorbid with schizophrenia, and the etiology of the comorbidity is unknown. To determine whether there is a genetic correlation of smoking behavior with schizophrenia, genome-wide association study (GWAS) meta-analysis results from five smoking phenotypes (ever/never smoker (N=74,035), age of onset of smoking (N=28,647), cigarettes smoked per day (CPD, N=38,860), nicotine dependence (N=10,666), and current/former smoker (N=40,562)) were compared to GWAS meta-analysis results from schizophrenia (N=79,845) using linkage disequilibrium (LD) score regression. First, the SNP heritability (h) of each of the smoking phenotypes was computed using LD score regression (ever/never smoker h=0.

Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis.

Background: Recent meta-analyses show that individuals with high risk variants in CHRNA5 on chromosome 15q25 are likely to develop lung cancer earlier than those with low-risk genotypes. The same high-risk genetic variants also predict nicotine dependence and delayed smoking cessation. It is unclear whether smoking cessation confers the same benefits in terms of lung cancer risk reduction for those who possess CHRNA5 risk variants versus those who do not.

Pathways to precision medicine in smoking cessation treatments.

Cigarette smoking is highly addictive and modern genetic research has identified robust genetic influences on nicotine dependence. An important step in translating these genetic findings to clinical practice is identifying the genetic factors affecting smoking cessation in order to enhance current smoking cessation treatments. We reviewed the significant genetic variants that predict nicotine dependence, smoking cessation, and response to cessation pharmacotherapy.

CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis.

Background: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis.

Methods: Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072).

Managing heart failure in the long-term care setting: nurses' experiences in Ontario, Canada.

Background: Implementation of heart failure guidelines in long-term care (LTC) settings is challenging. Understanding the conditions of nursing practice can improve management, reduce suffering, and prevent hospital admission of LTC residents living with heart failure.

Objective: The aim of the study was to understand the experiences of LTC nurses managing care for residents with heart failure.

Conservation of linkage and evolution of developmental function within the Tbx2/3/4/5 subfamily of T-box genes: implications for the origin of vertebrate limbs.

T-box genes encode a family of DNA-binding transcription factors implicated in numerous developmental processes in all metazoans. The Tbx2/3/4/5 subfamily genes are especially interesting because of their key roles in the evolution of vertebrate appendages, eyes, and the heart, and, like the Hox genes, the longevity of their chromosomal linkage. A BAC library derived from the single male amphioxus (Branchiostoma floridae) used to sequence the amphioxus genome was screened for AmphiTbx2/3 and AmphiTbx4/5, yielding two independent clones containing both genes.

The amphioxus genome and the evolution of the chordate karyotype.

Lancelets ('amphioxus') are the modern survivors of an ancient chordate lineage, with a fossil record dating back to the Cambrian period. Here we describe the structure and gene content of the highly polymorphic approximately 520-megabase genome of the Florida lancelet Branchiostoma floridae, and analyse it in the context of chordate evolution. Whole-genome comparisons illuminate the murky relationships among the three chordate groups (tunicates, lancelets and vertebrates), and allow not only reconstruction of the gene complement of the last common chordate ancestor but also partial reconstruction of its genomic organization, as well as a description of two genome-wide duplications and subsequent reorganizations in the vertebrate lineage.

The amphioxus T-box gene, AmphiTbx15/18/22, illuminates the origins of chordate segmentation.

Amphioxus and vertebrates are the only deuterostomes to exhibit unequivocal somitic segmentation. The relative simplicity of the amphioxus genome makes it a favorable organism for elucidating the basic genetic network required for chordate somite development. Here we describe the developmental expression of the somite marker, AmphiTbx15/18/22, which is first expressed at the mid-gastrula stage in dorsolateral mesendoderm.

Developmental expression of the amphioxus Tbx1/ 10 gene illuminates the evolution of vertebrate branchial arches and sclerotome.

We have isolated an amphioxus T-box gene that is orthologous to the two vertebrate genes, Tbx1 and Tbx10, and examined its expression pattern during embryonic and early larval development. AmphiTbx1/ 10 is first expressed in branchial arch endoderm and mesoderm of developing neurulae, and in a bilateral, segmented pattern in the ventral half of newly formed somites. Branchial expression is restricted to the first three branchial arches, and disappears completely by 4 days post fertilization.

Phylogenetic analysis of new plant myosin sequences.

We have sampled a large number of plant taxa, ranging from brown algae to angiosperms, for the presence of myosin sequences. Using phylogenetic analysis, we show that all but two of the new plant myosin sequences fall into two of three preexisting myosin classes. We identified two outlying sequences, which do not fall into any preexisting myosin class.

Phylogenetic analyses alone are insufficient to determine whether genome duplication(s) occurred during early vertebrate evolution.

The widely accepted notion that two whole-genome duplications occurred during early vertebrate evolution (the 2R hypothesis) stems from the fact that vertebrates often possess several genes corresponding to a single invertebrate homolog. However the number of genes predicted by the Human Genome Project is less than twice as many as in the Drosophila melanogaster or Caenorhabditis elegans genomes. This ratio could be explained by two rounds of genome duplication followed by extensive gene loss, by a single genome duplication, by sequential local duplications, or by a combination of any of the above.

Analysis of the small GTPase gene superfamily of Arabidopsis.

Small GTP-binding proteins regulate diverse processes in eukaryotic cells such as signal transduction, cell proliferation, cytoskeletal organization, and intracellular membrane trafficking. These proteins function as molecular switches that cycle between "active" and "inactive" states, and this cycle is linked to the binding and hydrolysis of GTP. The Arabidopsis genome contains 93 genes that encode small GTP-binding protein homologs.

Evolution of developmental functions by the Eomesodermin, T-brain-1, Tbx21 subfamily of T-box genes: insights from amphioxus.

We have identified an amphioxus T-box gene that is orthologous to the Eomesodermin, T-brain-1, and Tbx21 genes of vertebrates, and we have characterized its expression pattern during embryonic and larval development. AmphiEomes/Tbr1/Tbx21 is maternally expressed in oocytes and cleavage stage embryos. After the onset of zygotic transcription at the blastula stage, it is expressed in invaginating mesendoderm cells during gastrulation, but it is downregulated in presumptive ectoderm and neurectoderm.