Joanne M. Meyer

Bio: Joanne M. Meyer is an academic researcher from Novartis. The author has contributed to research in topics: Twin study & Population. The author has an hindex of 53, co-authored 108 publications receiving 13590 citations. Previous affiliations of Joanne M. Meyer include Millennium Pharmaceuticals & VCU Medical Center.

Genome-Wide Association Analysis Identifies Loci for Type 2 Diabetes and Triglyceride Levels

Abstract: New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D-in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1-and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.

Co-occurrence of Abuse of Different Drugs in Men The Role of Drug-Specific and Shared Vulnerabilities

Abstract: Background Previous research has demonstrated genetic and environmental influences on abuse of individual substances, but there is less known about how these factors may influence the co-occurrence of abuse of different illicit drugs. Methods We studied 3372 male twin pairs from the Vietnam Era Twin Registry. They were interviewed using the Diagnostic Interview Schedule, Version III, Revised to investigate the extent to which the abuse of different categories of drugs occurs together within an individual, as well as the possibility that genetic and environmental factors are responsible for observed co-occurrence. Co-occurrence was quantified using odds ratios and conditional probabilities. Multivariate biometrical modeling analyses were used to assess genetic and environmental influences on co-occurrence. Results Abusing any category of drug was associated with a marked increase in the probability of abusing every other category of drugs. We found evidence for a shared or common vulnerability factor that underlies the abuse of marijuana, sedatives, stimulants, heroin or opiates, and psychedelics. This shared vulnerability is influenced by genetic, family environmental, and nonfamily environmental factors, but not every drug is influenced to the same extent by the shared vulnerability factor. Marijuana, more than other drugs, was influenced by family environmental factors. Each category of drug, except psychedelics, had genetic influences unique to itself (ie, not shared with other drug categories). Heroin had larger genetic influences unique to itself than did any other drug. Conclusion There are genetically and environmentally determined characteristics that comprise a shared or common vulnerability to abuse a range of illicit drugs.

Epigenetic Modification of the FMR1 Gene in Fragile X Syndrome Is Associated with Differential Response to the mGluR5 Antagonist AFQ056

Abstract: Fragile X syndrome (FXS) is an X-linked condition associated with intellectual disability and behavioral problems. It is caused by expansion of a CGG repeat in the 5′ untranslated region of the fragile X mental retardation 1 (FMR1) gene. ThismutationisassociatedwithhypermethylationattheFMR1promoterandresultanttranscriptionalsilencing.FMR1 silencinghasmanyconsequences,includingup-regulationofmetabotropicglutamatereceptor5(mGluR5)–mediated signaling. mGluR5 receptor antagonists have shown promise in preclinical FXS models and in one small open-label study of FXS. We examined whether a receptor subtype–selective inhibitor of mGluR5, AFQ056, improves the behavioral symptoms of FXS in a randomized, double-blind, two-treatment, two-period, crossover study of 30 male FXS patients aged 18 to 35 years. We detected no significant effects of treatment on the primary outcome measure, the Aberrant Behavior Checklist–Community Edition (ABC-C) score, at day 19 or 20 of treatment. In an exploratory analysis, however, seven patients with full FMR1 promoter methylation and no detectable FMR1 messenger RNA improved, as measured with the ABC-C, significantly more after AFQ056 treatment than with placebo (P <0 .001). We detected no response in 18 patients with partial promoter methylation. Twenty-four patients experienced an adverse event, which was mostly mild to moderately severe fatigue or headache. If confirmed in larger and longer-term studies, these results suggest that blockade of the mGluR5 receptor in patients with full methylation at the FMR1 promoter may show improvement in the behavioral attributes of FXS.

Genetics and Developmental Psychopathology: 2. The Main Effects of Genes and Environment on Behavioral Problems in the Virginia Twin Study of Adolescent Behavioral Development

Abstract: Little is known about the contribution of genetic and environmental factors to risk for juvenile psychopathology. The Virginia Twin Study of Adolescent Behavioral Development allows these contributions to be estimated. A population-based, unselected sample of 1412 Caucasian twin pairs aged 8-16 years was ascertained through Virginia schools. Assessment of the children involved semi-structured face-to-face interviews with both twins and both parents using the Child and Adolescent Psychiatric Assessment (CAPA). Self-report questionnaires were also completed by parents, children, and teachers. Measures assessed DSM-III-R symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Conduct Disorder, Oppositional Defiant Disorder, Overanxious Disorder, Separation Anxiety, and Depressive Disorder. Factorially derived questionnaire scales were also extracted. Scores were normalized and standardized by age and sex. Maximum likelihood methods were used to estimate contributions of additive and nonadditive genetic effects, the shared and unique environment, and sibling imitation or contrast effects. Estimates were tested for heterogeneity over sexes. Generally, monozygotic (MZ) twins correlated more highly than dizygotic (DZ) twins, parental ratings more than child ratings, and questionnaire scales more highly than interviews. DZ correlations were very low for measures of ADHD and DZ variances were greater than MZ variances for these variables. Correlations sometimes differed between sexes but those for boy-girl pairs were usually similar to those for like-sex pairs. Most of the measures showed small to moderate additive genetic effects and moderate to large effects of the unique individual environment. Measures of ADHD and related constructs showed marked sibling contrast effects. Some measures of oppositional behavior and conduct disorder showed shared environmental effects. There were marked sex differences in the genetic contribution to separation anxiety, otherwise similar genetic effects appear to be expressed in boys and girls. Effects of rater biases on the genetic analysis are considered. The study supports a widespread influence of genetic factors on risk to adolescent psychopathology and suggests that the contribution of different types of social influence may vary consistently across domains of measurement.

PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

Abstract: Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.

Prevalence, Severity, and Comorbidity of 12-Month DSM-IV Disorders in the National Comorbidity Survey Replication

Abstract: Background Little is known about the general population prevalence or severity of DSM-IV mental disorders. Objective To estimate 12-month prevalence, severity, and comorbidity of DSM-IV anxiety, mood, impulse control, and substance disorders in the recently completed US National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using a fully structured diagnostic interview, the World Health Organization World Mental Health Survey Initiative version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents 18 years and older. Main Outcome Measures Twelve-month DSM-IV disorders. Results Twelve-month prevalence estimates were anxiety, 18.1%; mood, 9.5%; impulse control, 8.9%; substance, 3.8%; and any disorder, 26.2%. Of 12-month cases, 22.3% were classified as serious; 37.3%, moderate; and 40.4%, mild. Fifty-five percent carried only a single diagnosis; 22%, 2 diagnoses; and 23%, 3 or more diagnoses. Latent class analysis detected 7 multivariate disorder classes, including 3 highly comorbid classes representing 7% of the population. Conclusion Although mental disorders are widespread, serious cases are concentrated among a relatively small proportion of cases with high comorbidity.

Subjective Well-Being: Three Decades of Progress

Abstract: W. Wilson's (1967) review of the area of subjective well-being (SWB) advanced several conclusions regarding those who report high levels of "happiness". A number of his conclusions have been overturned: youth and modest aspirations no longer are seen as prerequisites of SWB. E. Diener's (1984) review placed greater emphasis on theories that stressed psychological factors. In the current article, the authors review current evidence for Wilson's conclusions and discuss modern theories of SWB that stress dispositional influences, adaptation, goals, and coping strategies. The next steps in the evolution of the field are to comprehend the interaction of psychological factors with life circumstances in producing SWB, to understand the causal pathways leading to happiness, understand the processes underlying adaptation to events, and develop theories that explain why certain variables differentially influence the different components of SWV (life satisfaction, pleasant affect, and unpleasant affect).

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

Abstract: There is increasing evidence that genome-wide association ( GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study ( using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined similar to 2,000 individuals for each of 7 major diseases and a shared set of similar to 3,000 controls. Case-control comparisons identified 24 independent association signals at P < 5 X 10(-7): 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn's disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals ( including 58 loci with single-point P values between 10(-5) and 5 X 10(-7)) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.

Subjective well-being: Three decades of progress

Abstract: W Wilson's (1967) review of the area of subjective well-being (SWB) advanced several conclusions regarding those who report high levels of "happiness" A number of his conclusions have been overturned: youth and modest aspirations no longer are seen as prerequisites of SWB E Diener's (1984) review placed greater emphasis on theories that stressed psychological factors In the current article, the authors review current evidence for Wilson's conclusions and discuss modern theories of SWB that stress dispositional influences, adaptation, goals, and coping strategies The next steps in the evolution of the field are to comprehend the interaction of psychological factors with life circumstances in producing SWB, to understand the causal pathways leading to happiness, understand the processes underlying adaptation to events, and develop theories that explain why certain variables differentially influence the different components of SWB (life satisfaction, pleasant affect, and unpleasant affect) In 1967, Warner Wilson presented a broad review of subjective well-being (SWB) research entitled, "Correlates of Avowed Happiness" Based on the limited data available at that time, Wilson concluded that the happy person is a "young, healthy, welleducated, well-paid, extroverted, optimistic, worry-free, religious, married person with high self-esteem, job morale, modest aspirations, of either sex and of a wide range of intelligence" (p 294) In the three decades since Wilson's review, investigations into SWB have evolved Although researchers now know a great deal more about the correlates of SWB, they are less interested in simply describing the demographic characteristics that correlate with it Instead, they focus their effort on understanding the processes that underlie happiness This trend represents a greater recognition of the central role played by people's goals, coping efforts, and dispositions In this article, we review research on several major theoretical approaches to well-being and then indicate how these theories clarify the findings on demographic correlates of SWB Throughout the review we suggest four directions that researchers should pursue in the decades ahead These are by no means the only questions left to answer, but we believe they are the most interesting issues left to resolve First, the causal direction of the correlates of happiness must be examined through more sophisticated methodologies Although the causal priority of demographic factors such as marriage and income is intuitively appealing, it is by no means certain Second, researchers must focus greater attention on the interaction between internal factors (such as personality traits) and external circumstances As we shall see, demographic factors have surprisingly small effects on SWB, but these effects may depend on the personalities of those individuals being studied Thus, future research must take Person X Situation interactions into account Third, researchers must strive to understand the processes underlying adaptation Considerable adaptation to both good and bad circumstances often occurs, yet the processes responsible for these effects are poorly understood Research that examines how habituation, coping strategies, and changing goals influence adaptation will shed much light on the processes responsible for SWB Finally, theories must be refined to make specific predictions about how input variables differentially influence the components of SWB In the past, many researchers have treated SWB as a monolithic entity, but it is now clear that there are separable components that exhibit unique patterns of relations with different variables In each section of this article we discuss progress and opportunities in these four areas