Publications (17)44.74 Total impact
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Article: Association between DRD2/ANKK1 Taq1A genotypes, depression and smoking cessation with nicotine replacement therapy.
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ABSTRACT: Tobacco dependence and depression are believed to have a common familial component, most probably genetic, and mood disorders have been reliably associated with failure to stop smoking. Variant genotypes of the Taq1A (DRD2/ANKK1, 32806T, rs1800497) polymorphism have been associated with failure to stop smoking in some studies, but not others. We investigated the association between Taq1A genotypes and smoking cessation, while also considering mental health. This was a prospective study in 419 smokers who attended a smoking cessation clinic and used standard doses of nicotine replacement therapy. DNA samples and baseline measures including demographics, severity of tobacco dependence, mental health history and history of drug misuse were taken. Smoking cessation at the end of treatment was biochemically verified using expired-air carbon monoxide. We found no simple relation between Taq1A genotype and smoking cessation, although the association between cessation and lifetime depression was significantly modified by genotype. The relationship was such that for those having only common alleles there was no association between depression and stopping smoking, whereas for those with at least one variant allele (A1A2/A1A1) depression was associated with a two-fold reduction in the likelihood of stopping. Those having a Taq1A variant allele and a history of depression are likely to experience particular difficulty when trying to stop smoking and may require treatment other than standard doses of nicotine replacement. This finding might explain previous conflicting results for Taq1A and smoking cessation in studies where depression history was not measured, and may help to explain the underlying link between depression and smoking.Pharmacogenetics and Genomics 04/2011; 21(8):447-53. · 3.48 Impact Factor -
Article: Gender-specific interactions between alcohol metabolism genes and severity of quantitative alcohol-related-traits in a Tibetan population.
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ABSTRACT: Association between genes influencing alcohol metabolism and alcohol use disorders (AUD) has been extensively studied, but the effect of interactions between these genes and AUD have rarely been tested. Our previous case-control study in a Tibetan population noted that the positive association between c2 allele of cytochrome P4502E1 (CYP2E1) gene and AUD might only exist in males who are homozygotes for 1 alleles of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B) genes, but this interaction did not reach statistical significance. Using the same set of data, the present study was aimed at exploring interactions between these genes and quantitative alcohol-related-trait scores (QARTs), and whether these are influenced by gender. The sample included 383 AUD cases with the alcohol use disorders identification test (AUDIT) score ≥10 and 350 normal controls with the AUDIT score ≤5. QARTs were measured using three factors from AUDIT. Possible associations of QARTs with interactions among genotypes of ALDH2 1/ 2, ADH1B1/2 and CYP2E1 c1/c2 and sex were analyzed in AUD cases and normal controls separately. The subjects with 2 alleles of ALDH2 or/and ADH1B had significantly lower scores of alcohol intake among controls but had significantly higher scores of alcohol related problems among cases. The score of alcohol intake in male cases who are homozygous for ALDH2 1 and ADH1B 1 and with CYP2E1 c2 allele was significantly higher than that of other cases. These findings suggest that interactions between genes influencing alcohol metabolism are influenced by gender and might affect QARTs differently between the milder-/non-drinkers and AUD cases.Neuroscience Letters 03/2011; 495(1):22-5. · 2.11 Impact Factor -
Article: Interaction among genes influencing ethanol metabolism and sex is association with alcohol use disorders in a Tibet population.
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ABSTRACT: Associations between alcohol use disorders and polymorphisms of genes influencing ethanol metabolism have been widely reported, but gene-gene and gene-sex interaction studies have rarely been examined. Using a set of samples collected during an epidemiological study of alcohol use disorders AUDs in a Tibetan population in China, we performed a case-control study to investigate the relationship between the functional polymorphisms of genes influencing ethanol metabolism and AUDs. The sample included 383 individuals with an AUDIT score >or=10 and 350 control subjects with the AUDIT score <or=5. All participants were genotyped for ALDH2*1/*2, ADH1B*1/*2, and CYP2E1*c1/c2*. Data were analyzed employing an integrated strategy using MDR, SPSS, and UNPHASED software. The MDR analysis showed that the four-factor model including ADH1B*1/*2, ALDH2*1/*2, and CYP2E1*c1/*c2 polymorphisms, and sex was the most accurate model associated with AUDs with the highest OR 3.299. It also revealed that CYP2E1 *c1/*c2 polymorphism interacted significantly with sex. Independent analysis confirmed that both ADH2*2 and ALDH2*2 allele were significantly associated with AUDs (OR: 0.441 for ADH2*2 and 0.137 for ALDH2*2). CYP2E1*c2 was positively associated with AUDs only in males homozygotic for ALDH2*1 and ADH1B*1 (OR: 2.585). Cumulative association analysis showed the number of protective alleles and genotypes were negatively associated with AUDs. In conclusion, ALDH2*2 and ADH1B*2 alleles were not only independently associated with AUDs but also demonstrated cumulative dosage effects. However the positive association between CYP2E1*c2 allele and AUDs might only exist in males homozygotic for ALDH2*1 and ADH1B*1.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2009; 153B(2):561-9. · 3.70 Impact Factor -
Article: Binge drinking trends in a UK community‐based sample
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ABSTRACT: Aims To investigate binge drinking trends using unrelated singletons from the GENESiS sample, aged 20–60 years.Methods The GENESiS study is a questionnaire study based in the UK and includes measures on various mental health items as well as measures of alcohol consumption. Alcohol data from 20 062 subjects were analysed with respect to binge/heavy drinking behaviour as defined by the Office for National Statistics, UK.Results The average number of units of alcohol per week consumed was 16 for men and 8 for women. Female binge drinking (more than 6 units per drinking session) was found to be very comparable to male binge drinking (more than 8 units per drinking session) with 15% of males reporting binge drinking compared with 18% of females. Binge drinking was found to be most prevalent amongst males and females in their twenties (33% of males vs 38% of females).Conclusions This study revealed that, for both men and women, there was evidence of substantial numbers drinking heavily and in a binge drinking pattern, particularly in young adults.07/2009; 8(4):234-237. -
Article: An epidemiological survey of alcohol use disorders in a Tibetan population.
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ABSTRACT: We performed an epidemiological survey in order to detect the prevalence of alcohol use disorders in a sub-group of the population of Tibet. The Alcohol Use Disorders Identification Test (AUDIT) questionnaire, the Severity of Alcohol Dependence Questionnaire (SADQ), and a 12-item version of the General Health Questionnaire (GHQ12) were used to obtain epidemiological data on alcohol use disorders and to assess the severity of 'problem drinking' and general mental health status. The AUDIT is a reliable and valid screening tool for both alcohol abuse and dependence in the Tibetan population to identify individuals with alcohol use problems. The cut-off points were set to be 10 and 13 of the AUDIT scores as a diagnostic discriminator of alcohol abuse and alcohol dependence, respectively, with both sensitivity and specificity>0.84. The prevalence of alcohol abuse, was 2.7% (female: 2.0%; male: 6.2%), alcohol dependence 13.5% (female: 7.6%; male: 25.4%) and alcohol use disorders 16.2% (female: 9.6%; male: 31.6%). Age and sex were the main factors affecting an individual's alcohol use and general mental health status. The epidemiological data on alcohol use disorders documented in this project may be helpful in future work seeking more valid causal inferences or interpretations related to this prevalent health problem in Tibet.Psychiatry Research 05/2008; 159(1-2):56-66. · 2.52 Impact Factor -
Article: Functional polymorphism of CYP2E1 gene and alcohol use disorders in a Tibetan population.
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ABSTRACT: To investigate the relationship between the CYP2E1*c1/*c2 polymorphism and alcohol use disorders, and the potential influence of the CYP2E1*c1/*c2 polymorphism on the severity and dimensions of alcohol use disorders in Tibetan. Three hundred and forty Tibetans with Alcohol Use Disorders Identification Test (AUDIT) score >or=10 and another 315 matched control subjects with AUDIT score <or=5 were enrolled. The CYP2E1*c1/*c2 polymorphism was determined by the standard PCR-RFLP method. The frequency of the CYP2E1*c2 allele in subjects with alcohol use disorders (16.2%) was significantly higher than that of the controls (10.8%), with a P value of 0.005 and OR value of 1.60 (95% CI: 1.15 approximately 2.21). There was also a significant difference in genotype frequencies between the 2 groups (chi2=8.75, P=0.01). Subjects with alcohol use disorders had higher frequencies of genotypes with at least one copy of allele c2 (28.5% vs. 18.7%; chi2=8.65, P=0.003; OR=1.73) than the control group. The association of CYP2E1*c2 allele with alcohol use disorders was much stronger in males than in females, with a male OR value of 2.30. CYP2E1*c2 allele was associated with increased alcohol consumption and alcohol use disorders in males. There is the positive association among CYP2E1*c2 allele, alcohol use disorders, and the amount of alcohol consumption in Tibetan population.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 04/2008; 33(4):284-92. -
Article: Association of the serotonin transporter gene, neuroticism and smoking behaviours.
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ABSTRACT: Cigarette consumption and smoking cessation are influenced in part by genes. Personality traits have also been implicated in the aetiology of smoking. Neuroticism, a personality trait with a heritable component, correlates well with anxiety and depression, increasing the risk of being a smoker and decreasing the chance of smoking cessation. Several prior studies in non-British populations have given conflicting results as to whether some genetic polymorphisms affect the relationship between smoking and neuroticism. This study investigated the influence of serotonin transporter (5HTTLPR) genotypes on a composite measure of neuroticism and cigarette consumption/smoking cessation in a British population. Although neuroticism was significantly associated with cigarette consumption and smoking cessation, genotype did not affect this relationship. Our results do not support initial interest in utilising 5HTTLPR genotypes in combination with neuroticism ratings for predicting outcome in smoking cessation clinical settings.Journal of Human Genetics 02/2008; 53(3):239-46. · 2.57 Impact Factor -
Article: Dopamine transporter polymorphisms are associated with short-term response to smoking cessation treatment.
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ABSTRACT: To examine the association between polymorphisms in the dopamine transporter gene (SLC6A3, DAT1) and treatment outcome in smokers attempting to quit using either nicotine replacement therapy or bupropion. The sample consisted of 583 smokers recruited from a smoking cessation clinic, and followed throughout the 4 weeks of post-cessation treatment with behavioural support and either nicotine replacement therapy or bupropion. At 1 week after smoking cessation, the 3' untranslated region (3'UTR) variable number of tandem repeats (VNTRs) and the 30-bp intron 8 VNTR DAT1 genotypes were associated with the ability to stop smoking (3'UTR VNTR, odds ratio=2.0, 95% confidence interval=1.2-3.5, novel intron 8 VNTR, odds ratio=1.8, 95% confidence interval=1.0-2.9), controlling for potential confounders. The results were weaker and no longer significant at a 4-week follow-up. We find evidence, although modest, of a medium-sized effect of DAT1 genotype on the ability to stop smoking early in a smoking cessation attempt. If the effect is real, and is strongest in the very early stages of smoking cessation, this suggests that the primary utility of DAT1 screening in this field will be in the identification of those most at risk of early relapse after quitting.Pharmacogenetics and Genomics 02/2007; 17(1):61-7. · 3.48 Impact Factor -
Article: Morbid risk for psychiatric disorder among the relatives of methamphetamine users with and without psychosis.
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ABSTRACT: It is not clear why some methamphetamine (MAMP) abusers develop psychotic symptoms, while others use MAMP regularly over long periods and remain unscathed. We tested the hypotheses that those users who develop MAMP-induced psychosis (MIP) have greater familial loading for psychotic disorders than users with no psychosis. Four hundred forty-five MAMP users were recruited from a psychiatric hospital and a detention center in Taipei, and were assessed with the Diagnostic Interview for genetic studies (DIGS-C) and the Family Interview for genetic study (FIGS-C). Morbid risk (MR) for psychiatric disorders in first-degree relatives was compared between those MAMP users with a lifetime diagnosis of MAMP psychosis and those without. The relatives of MAMP users with a lifetime diagnosis of MAMP psychosis had a significantly higher MR for schizophrenia (OR = 5.4, 95% CI: 2.0-14.7, P < 0.001) than the relatives of those probands who never became psychotic. Furthermore, the MR for schizophrenia in the relatives of the subjects with a prolonged MAMP psychosis (MIP-P) was higher than in the relatives of those users with a brief MAMP psychosis (MIP-B) (OR = 2.8, 95% CI: 1.0-8.0, P = 0.042). The greater his or her familial loading for schizophrenia, the more likely a MAMP user is to develop psychosis, and the longer that psychosis is likely to last.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2005; 136B(1):87-91. · 3.70 Impact Factor -
Article: Genome-wide linkage analysis of a composite index of neuroticism and mood-related scales in extreme selected sibships.
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ABSTRACT: There is considerable evidence to suggest that the genetic vulnerabilities to depression and anxiety substantially overlap and quantitatively act to alter risk to both disorders. Continuous scales can be used to index this shared liability and are a complementary approach to the use of clinical phenotypes in the genetic analysis of depression and anxiety. The aim of this study (Genetic and Environmental Nature of Emotional States in Siblings) was to identify genetic variants for the liability to depression and anxiety after the application of quantitative genetic methodology to a large community-based sample (n = 34,371), using four well-validated questionnaires of depression and anxiety. Genetic model fitting was performed on 2658 unselected sibships, which provided evidence for a single common familial factor that accounted for a substantial proportion of the genetic variances and covariances of the four scales. Using the parameter estimates from this model, a composite index of liability (G) was constructed. This index was then used to select a smaller--but statistically powerful--sample for DNA collection (757 individuals, 297 sibships). These individuals were genotyped with more than 400 microsatellite markers. After the data were checked and cleaned, linkage analysis was performed on G and the personality scale of neuroticism using the regression-based linkage program MERLIN-REGRESS. The results indicated two potential quantitative trait loci (QTL): one on chromosome 1p (LOD 2.2) around 64 cM (43-70 cM) near marker D1S2892 and another on chromosome 6p (LOD 2.7) around 47 cM (34-63 cM) near marker D6S1610. Further exploratory sex-specific analyses suggested that these QTLs might have sex-limited effects.Human Molecular Genetics 11/2004; 13(19):2173-82. · 7.64 Impact Factor -
Article: Alcohol dependence and the alcohol Stroop paradigm: evidence and issues.
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ABSTRACT: Firstly to test alcohol abusers attentional bias towards alcohol-related stimuli. Secondly, to shed light onto other factors that may influence the alcohol Stroop effect by considering variables including mood status in the analyses. Finally, to examine severity of dependence on Stroop performance. Repeated measures with alcohol versus control group as the between participant factors and within participant factors were the reaction times to different types of stimuli. Standard multiple regression was used to determine predictors of Stroop performance. A repeated measures design was used with severity of dependence as the between participant factors and Stroop reaction times as the within participant factors. South and East London, UK. Sixty-four alcoholics in treatment and 64 community controls from general practice participated in the study. Alcohol dependence severity was measured using the SADQ, mood was measured with the POMS-SF and a computerised emotional Stroop task was employed to measure attentional bias. Regardless of demographic factors and mood status, alcoholics responded significantly slower to alcohol-related than neutral words when compared to controls. When severity of alcohol dependence was used as between participant factors, no significant differences were found with Stroop performance between high and low alcohol severity groups. Alcohol-related stimuli are distracting to heavy users of alcohol, independent of demographic, mood and dependence status. Findings offer insight into the development of alcohol dependence and the issues that surround the alcohol Stroop paradigm.Drug and Alcohol Dependence 10/2004; 75(3):225-31. · 3.38 Impact Factor -
Article: Association analysis of the DRD4 and COMT genes in methamphetamine abuse.
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ABSTRACT: We analyzed two polymorphisms in genes encoding proteins of the dopamine system, the Val158Met polymorphism in the catechol-O-methyltransferase gene and the 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene for association with methamphetamine abuse. We used a case/control design with 416 methamphetamine abusing subjects and 435 normal controls. All subjects were Han Chinese from Taiwan. We found an excess of the high activity Val158 allele in the methamphetamine abuser group, consistent with several previous reports of association of this allele with drug abuse. The 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene itself did not show significant association with methamphetamine abuse. However, analysis of the 120-bp VNTR polymorphism and the exon 3 VNTR in the dopamine D4 receptor as a haplotype showed significant association with methamphetamine abuse, which gave an empirical P value 0.0034 for a heterogeneity model. Moreover, there were significant interactive effects between polymorphisms in the catechol-O-methyltransferase and dopamine D4 genes. The evidence of interaction between COMT 158 Val/Met and DRD4 48-bp VNTR polymorphisms (P = 0.0003, OR = 1.45, 95% CI: 1.148-1.77), and between COMT 158 Val/Met and DRD4 120 bp promoter polymorphisms (P = 0.01, OR = 1.10, 95% CI: 1.10-1.18) were significant but the latter was weak. We conclude that genetic variation in the dopamine system may encode an additive effect on risk of becoming a methamphetamine abuser.American Journal of Medical Genetics Part B Neuropsychiatric Genetics 09/2004; 129B(1):120-4. · 3.70 Impact Factor -
Article: Psychiatric comorbidity and gender differences of persons incarcerated for methamphetamine abuse in Taiwan.
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ABSTRACT: Methamphetamine (MAP) abuse has been common in Taiwan for the past decade. The purpose of the present study was to investigate MAP abuse in Taiwan, with specific attention to psychiatric comorbidity and gender differences. A total of 325 MAP abuse subjects (180 male, 145 female) from a detention center in Taipei were assessed with the Diagnostic Interview for Genetic Studies. The following were studied: drug use behavior, treatment-seeking behavior, lifetime prevalence of mood disorders, MAP psychosis, alcohol use disorders, pathological gambling and antisocial personality. The MAP-abuse subjects in Taiwan had high psychiatric morbidity and low access to mental health services. There also exist certain differences in the prevalence of psychiatric illnesses and treatment-seeking behavior between male and female subjects. Compared with their male counterparts, more female subjects reported experience of mental disturbance and experience of psychiatric treatment. The female subjects more commonly reported suicidal behaviors than the male subjects.Psychiatry and Clinical Neurosciences 05/2004; 58(2):206-12. · 2.13 Impact Factor -
Article: Psychiatric comorbidity and gender differences of persons incarcerated for methamphetamine abuse in Taiwan
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ABSTRACT: Abstract Methamphetamine (MAP) abuse has been common in Taiwan for the past decade. The purpose of the present study was to investigate MAP abuse in Taiwan, with specific attention to psychiatric comorbidity and gender differences. A total of 325 MAP abuse subjects (180 male, 145 female) from a detention center in Taipei were assessed with the Diagnostic Interview for Genetic Studies. The following were studied: drug use behavior, treatment-seeking behavior, lifetime prevalence of mood disorders, MAP psychosis, alcohol use disorders, pathological gambling and antisocial personality. The MAP-abuse subjects in Taiwan had high psychiatric morbidity and low access to mental health services. There also exist certain differences in the prevalence of psychiatric illnesses and treatment-seeking behavior between male and female subjects. Compared with their male counterparts, more female subjects reported experience of mental disturbance and experience of psychiatric treatment. The female subjects more commonly reported suicidal behaviors than the male subjects.Psychiatry and Clinical Neurosciences 03/2004; 58(2):206 - 212. · 2.13 Impact Factor -
Article: DNA by Mail: An Inexpensive and Noninvasive Method for Collecting DNA Samples from Widely Dispersed Populations
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ABSTRACT: As specific genes are identified that are associated with behavior, it becomes increasingly important for behavioral geneticists to be able to incorporate these genes in their research. Rather than using blood, DNA can be extracted from cheek swabs, which makes it possible to obtain DNA inexpensively by mail from large, widely dispersed individuals. The purpose of this paper is to recommend this technique to the behavioral genetics community and to present results of our use of this technique to obtain DNA by mail for 114 2-year-olds and 116 adults.Behavior Genetics 04/1997; 27(3):251-257. · 2.52 Impact Factor -
Article: The serotonin transporter gene and peer-rated neuroticism
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ABSTRACT: POLYMORPHISMS in the serotonin transporter gene (5HTT) have been reported to be associated with neuroticism (emotionality) and with depression. A recent report of an association between 5HTT and neuroticism involved unselected samples and self-report questionnaires.1 We attempted to extend these findings using a selected extremes design and peer ratings. From a sample of 2085 individuals, each assessed on neuroticism by two independent peers, we selected 52 individuals from the top 5% and 54 individuals from the bottom 5%. No association was found for either a functional 44 bp insertion/deletion polymorphism in 5HTT regulatory sequence (5HTTLPR) or for a non-functional variable number tandem repeat 5HTT polymorphism.Neuroreport 03/1997; 8(5):1301-1304. · 1.66 Impact Factor -
Article: Role of the GABAAβ2, GABAAα6, GABAAα1 and GABAAγ2 receptor subunit genes cluster in drug responses and the development of alcohol dependence
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ABSTRACT: γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter of the central nervous system and it acts at the GABAA and GABAB receptors. A possible role for the GABAA receptors in alcohol action has been derived from in vitro cell models, animal studies and human research. GABAA subunit mRNA expression in cell models has suggested that the long form of the γ2 subunit is essential for ethanol enhanced potentiation of GABAA receptors, by phosphorylation of a serine contained within the extra eight amino acids. Several animal studies have demonstrated that alterations in drug and alcohol responses may be caused by amino-acid differences at the GABAAα6 and GABAAγ2 subunits. An Arg100/Glu100 change at the GABAAα6 subunit conferring altered binding efficacy of the benzodiazepine inverse agonist Ro 15–4513, was found between the AT (alcohol tolerance) and ANT (alcohol non-tolerance) rats. Several loci related to alcohol withdrawal on mouse chromosome 11 which corresponds to the region containing four GABAA subunit (β2, α6, α1 and γ2) genes on human chromosome 5q33–34, were also identified. Gene knockout studies of the role of GABAAα6 and GABAAγ2 subunit genes in mice have demonstrated an essential role in the modulation of other GABAA subunit expression and the efficacy of benzodiazepine binding. Absence of the GABAAγ2 subunit gene has more severe effects with many of the mice dying shortly after birth. Disappointingly few studies have examined the effects of response to alcohol in these gene knockout mice. Human genetic association studies have suggested that the GABAAβ2, α6, α1 and γ2 subunit genes have a role in the development of alcohol dependence, although their contributions may vary between ethnic group and phenotype. In summary, in vitro cell, animal and human genetic association studies have suggested that the GABAAβ2, α6, α1 and γ2 subunit genes have an important role in alcohol related phenotypes (300 words).Neurochemistry International.
Top co-authors
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Institutions
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2011
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University College London
- Department of Epidemiology and Public Health
London, ENG, United Kingdom
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2008–2011
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Sichuan University
Chengdu, Sichuan Sheng, China
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2007
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King's College London
- Institute of Psychiatry
London, ENG, United Kingdom
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2004
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London Metropolitan University
- School of Psychology
London, ENG, United Kingdom
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