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1.
Mol Psychiatry ; 23(3): 666-673, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28439101

RESUMO

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.


Assuntos
Esquizofrenia/genética , Transtornos de Estresse Pós-Traumáticos/genética , Adulto , Negro ou Afro-Americano/genética , Transtorno Bipolar/genética , Estudos de Casos e Controles , Transtorno Depressivo Maior/genética , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais , População Branca/genética
2.
J Eur Acad Dermatol Venereol ; 31(7): 1223-1228, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28129487

RESUMO

BACKGROUND: Growing evidence suggests that some individuals may exhibit symptoms of dependence on ultraviolet (UV) light, a known carcinogen, in the context of tanning; however, few studies have investigated predictors of tanning dependence (TD). OBJECTIVE: To identify predictors of TD. METHODS: Non-Hispanics of European ancestry who had previously participated in a case-control study of early-onset basal cell carcinoma completed an online survey to ascertain TD and other behaviours (alcohol dependence, nicotine dependence, seasonal affective disorder (SAD), exercise 'addiction' and depression). Information on host factors, such as skin and eye colour and history of sunbathing and indoor tanning, was obtained from a study in which the participants were previously enrolled. Lifetime TD was assessed using the modified Cut down, Annoyed, Guilty, Eye-opener (mCAGE) and the modified Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (mDSM-IV-TR) questionnaires. Participants were classified as 'TD' if positive on both questionnaires and not TD if negative on both questionnaires. RESULTS: In total, 499 individuals completed the online survey (81.9% participation rate), and 24.4% were classified as 'TD'. In the multivariate model, women were more likely to be TD [odds ratio (OR) 6.93; 95% confidence intervals (95% CI) (3.36-14.27)] than men. Alcohol dependence (OR 6.55: 95% CI 3.19-13.42), SAD (OR 2.77; 95% CI 1.26-6.09) and exercise 'addiction' (OR 5.47; 95% CI 1.15-26.06) were all significant predictors for TD. CONCLUSION: Increased knowledge of those at risk for TD will allow appropriate interventions to be designed.


Assuntos
Comportamento Aditivo , Banho de Sol , População Branca , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino
3.
Comput Biomed Res ; 24(3): 234-48, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1868693

RESUMO

Parallel computers offer a solution to improve the lengthy computation time of many conventional, sequential programs used in molecular biology. On a parallel computer, different pieces of the computation are performed simultaneously on different processors. LINKMAP is a sequential program widely used by scientists to perform genetic linkage analysis. We have converted LINKMAP to run on a parallel computer, using the machine-independent parallel programming language, Linda. Using the parallelization of LINKMAP as a case study, the paper outlines an approach to converting existing highly iterative programs to a parallel form. The paper describes the steps involved in converting the sequential program to a parallel program. It presents performance benchmarks comparing the sequential version of LINKMAP with the parallel version running on different parallel machines. The paper also discusses alternative approaches to the problem of "load balancing," making sure the computational load is shared as evenly as possible among the available processors.


Assuntos
Mapeamento Cromossômico , Ligação Genética/genética , Biologia Molecular/métodos , Software , Previsões , Escore Lod , Linguagens de Programação , Design de Software
4.
Nature ; 347(6288): 80-3, 1990 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-1975640

RESUMO

Receptors for dopamine have been classified into two functional types, D1 and D2. They belong to the family of receptors acting through G (or guanine nucleotide-binding) proteins. D2 receptors inhibit adenylyl cyclase, but D1 receptors stimulate adenylyl cyclase and activate cyclic AMP-dependent protein kinases. Dopamine D1 and D2 receptors are targets of drug therapy in many psychomotor disorders, including Parkinson's disease and schizophrenia, and may also have a role in drug addiction and alcoholism. D1 receptors regulate neuron growth and differentiation, influence behaviour and modify dopamine D2 receptor-mediated events. We report here the cloning of the D1 receptor gene, which resides on an intronless region on the long arm of chromosome 5, near two other members of the G-linked receptor family. The expressed protein, encoded by 446 amino acids, binds drugs with affinities identical to the native human D1 receptor. The presence of a D1 receptor gene restriction fragment length polymorphism will be helpful for future disease linkage studies.


Assuntos
Cromossomos Humanos Par 5 , Receptores Dopaminérgicos/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Benzazepinas/metabolismo , Química Encefálica , Bovinos , Clonagem Molecular , Glicosilação , Humanos , Íntrons , Masculino , Dados de Sequência Molecular , Hibridização de Ácido Nucleico , Fosforilação , Polimorfismo de Fragmento de Restrição , RNA Mensageiro/análise , Ratos , Ratos Endogâmicos , Receptores de Dopamina D1 , Mapeamento por Restrição , Distribuição Tecidual , Transfecção
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