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Robert A Philibert – One of the best experts on this subject based on the ideXlab platform.
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Examination of the nicotine dependence (NICSNP) consortium findings in the Iowa Adoption Studies population.
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2009Co-Authors: Robert A Philibert, Nancy Hollenbeck, Tracy D. Gunter, Alexandre A. Todorov, Allan M. Andersen, Andrew C. Heath, Pamela A. F. MaddenAbstract:INTRODUCTION Nicotine dependence results from a complex interplay of genetic and environmental factors. Over the past several years, a large number of Studies have been performed to identify distinct gene loci containing genetic vulnerability to nicotine dependence. Two of the most prominent Studies were conducted by the Collaborative Study of the Genetics of Nicotine Dependence (NICSNP) Consortium using both candidate gene and high-density association approaches. METHODS We attempted to confirm and extend the most significant findings from the high-density association study and the candidate gene study using the behavioral and genetic resources of the Iowa Adoption Studies, the largest case-control Adoption study of substance use in the United States. RESULTS We found evidence that genetic variation at CHRNA1, CHRNA2, CHRNA7, and CHRNB1 alters susceptibility to nicotine dependence, but we did not replicate any of the most significant single nucleotide polymorphism associations from the NICSNP high-density association study. DISCUSSION Further examination of the NICSNP findings in other population samples is indicated.
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Role of GABRA2 on risk for alcohol, nicotine, and cannabis dependence in the Iowa Adoption Studies.
Psychiatric genetics, 2009Co-Authors: Robert A Philibert, Nancy Hollenbeck, Tracy D. Gunter, Allan M. Andersen, Steven R. H. Beach, Gene H. Brody, William AdamsAbstract:A number of Studies have demonstrated that genetic variation at GABRA2 alters vulnerability to alcohol dependence. However, the exact identity of the causal variant(s), the relationship of these variants to other forms of substance use and behavioral illness is uncertain. Therefore, we genotyped 516 subjects from the Iowa Adoption Studies, a large longitudinal case and control Adoption study of substance use, at 39 single nucleotide polymorphisms encompassing the GABRA2 locus and analyzed them with respect to their lifetime history of three common forms of substance use (alcohol (AD), nicotine (ND) and cannabis dependence (CD)), major depressive disorder (MDD) and antisocial personality disorder (ASPD) and relevant exposure variables. Using regression analysis, we found substantial evidence that both GABRA2 genotype and haplotype are significantly related to vulnerability to AD, ND and CD with the strongest relationships noted with respect to ND. Consistent with prior Studies suggesting exposure is an important step in the development of substance use, we found the inclusion of substance exposure data in to our analytic models markedly increased the strength of the genetic associations of GABRA2 haplotype with substance use. Finally, we report that the genetic effects were markedly more pronounced in females than in males. We conclude that genetic variation at or near the GABRA2 locus significantly effects vulnerability not only to AD, but to other forms of substance use including ND and CD, and that the effects may be sex dependent.
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The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies
American Journal of Medical Genetics, 2007Co-Authors: Robert A Philibert, Nancy Hollenbeck, William Adams, Harinder K. Sandhu, Tracy D. Gunter, Anup MadanAbstract:Serotonin Transporter (5HTTor SLC6A4) mRNA transcription is regulated by both genetic and epigenetic mechanisms. Unfortunately, despite intense scrutiny, the exact identity and contribution of each of these regulatory mechanisms, and their relationship to behavioral illness remain unknown. This lack of knowledge is critical because alterations in SLC6A4 function are posited to be central to a wide variety of CNS disorders. In order to address this shortcoming, we quantified 5HTTLPR genotype, SLC6A4 mRNA production and CpG methylation using biomaterial from 192 lymphoblast cell lines derived from subjects who participated in the latest wave of the Iowa Adoption Studies. We then analyzed the resulting data with respect to clinical characteristics. We confirmed prior findings that the short (s) 5HTTLPR allele is associated with lower amounts of mRNA transcription, but there was no significant effect of the “Long G” allele on mRNA transcription. We also found that CpG methylation was higher (P< 0.0008) and mRNA production (P< 0.0001) was lower in females as compared to males. Those subjects with a lifetime history of Alcohol Dependence had higher levels of SLC6A4 mRNA. There was a trend for an association of increased overall methylation with lifetime history of major depression. Finally, we confirm our prior findings that the exact levels of 5HTT mRNA expression are dependent on how it is measured. We conclude that both genetic variation and epigenetic modifications contribute to the regulation of SLC6A4 function and that more in-depth Studies of the molecular mechanisms controlling gene activity and the relationship of these mechanisms to behavioral illness are indicated.
Ming T Tsuang – One of the best experts on this subject based on the ideXlab platform.
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the molecular genetics of schizophrenia an emerging consensus
Expert Reviews in Molecular Medicine, 2002Co-Authors: Stephen V Faraone, Levi Taylor, Ming T TsuangAbstract:: Schizophrenia is perhaps the most debilitating mental disease and determining the underlying cause has become a challenging area of psychiatric research. It is relatively well established that genes play a role in the aetiology of schizophrenia. In this article, a review of important findings related to schizophrenia as a genetic trait will be provided, including a discussion of family, twin and Adoption Studies. Molecular genetic Studies of specific candidate genes are then reviewed. Some controversies within the literature are examined and possible directions for future research are discussed.
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Family, twin, and Adoption Studies of bipolar disease.
Current psychiatry reports, 2002Co-Authors: Levi Taylor, Stephen V Faraone, Ming T TsuangAbstract:Bipolar disease features states of severe depression that usually fluctuate with at least one episode of intense elation or mania. It is a disorder that has been thought for some time to have a heritable component. The lifetime prevalence of bipolar disease in the general population is approximately 1%. In contrast, family Studies have shown the approximate lifetime risk of a first-degree relative of a bipolar proband to be 5% to 10%. Moreover, Studies of monozygotic twins show that their risk of contracting the disease is as much as 75 times greater than that for the general population. In addition, Adoption Studies have demonstrated that biological relatives of bipolar patients are substantially more likely to have the disorder than are adoptive relatives.
Stephen V Faraone – One of the best experts on this subject based on the ideXlab platform.
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the molecular genetics of schizophrenia an emerging consensus
Expert Reviews in Molecular Medicine, 2002Co-Authors: Stephen V Faraone, Levi Taylor, Ming T TsuangAbstract:: Schizophrenia is perhaps the most debilitating mental disease and determining the underlying cause has become a challenging area of psychiatric research. It is relatively well established that genes play a role in the aetiology of schizophrenia. In this article, a review of important findings related to schizophrenia as a genetic trait will be provided, including a discussion of family, twin and Adoption Studies. Molecular genetic Studies of specific candidate genes are then reviewed. Some controversies within the literature are examined and possible directions for future research are discussed.
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Family, twin, and Adoption Studies of bipolar disease.
Current psychiatry reports, 2002Co-Authors: Levi Taylor, Stephen V Faraone, Ming T TsuangAbstract:Bipolar disease features states of severe depression that usually fluctuate with at least one episode of intense elation or mania. It is a disorder that has been thought for some time to have a heritable component. The lifetime prevalence of bipolar disease in the general population is approximately 1%. In contrast, family Studies have shown the approximate lifetime risk of a first-degree relative of a bipolar proband to be 5% to 10%. Moreover, Studies of monozygotic twins show that their risk of contracting the disease is as much as 75 times greater than that for the general population. In addition, Adoption Studies have demonstrated that biological relatives of bipolar patients are substantially more likely to have the disorder than are adoptive relatives.
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Dopamine D4 gene 7-repeat allele and attention deficit hyperactivity disorder.
The American journal of psychiatry, 1999Co-Authors: Stephen V Faraone, Joseph Biederman, Barbara Weiffenbach, Tim Keith, Monica P. Chu, Alix Weaver, Thomas J. Spencer, Timothy E. Wilens, Jean A. Frazier, Mario ClevesAbstract:OBJECTIVE: Family, twin, and Adoption Studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component, and some Studies have reported an association between ADHD and the dopamine D4 (DRD4) gene. METHOD: The authors recruited 27 triads that comprised an ADHD adult, his or her spouse, and their ADHD child. These triads were assessed for ADHD, and their DNA was genotyped for DRD4 alleles. RESULTS: A multiallelic transmission disequilibrium test suggested an association between ADHD and the DRD4 7-repeat allele. Among family members, the number of 7-repeat alleles predicted the diagnosis of ADHD. CONCLUSIONS: Prior reports of an association between ADHD and DRD4 generalize to families recruited through clinically referred ADHD adults. However, because there are some conflicting Studies, further work is needed to clarify the role of DRD4 in the etiology of the disorder.