Robert A Philibert
University Of Iowa
Project start date: 2008-07-01
Project end date: 2013-01-31
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EXAMINATION OF GENETIC AND GXE EFFECTS IN THE FAMILY AND COMMUNITY HEALTH STUDIES
Robert A Philibert
University Of Iowa, Iowa City, Ia 52242
Grant 5R01MH080898-03 from National Institute Of Mental Health
Abstract: The purpose of this grant application is to integrate a molecular genetics component to a currently funded study of the effects of behavioral and environmental factors on psychological well-being and diagnostic status of African-American (AA) subjects participating in the Family and Community Health Study (FACHS). The biomaterial for the proposed project will be collected from an existing sample of 771 African American families from Iowa and Georgia who were recruited to participate in the Family and Community Health Study (FACHS), all of whom had a child who was 10 to 11 years of age at the time of recruitment into the study in 1997. The data we have already collected from these women and their families provides a rich and extensive longitudinal foundation upon which to build the proposed project. The proposed use of previously validated genetic markers in addition to sensitive measures of context reduces error variance and capitalization on chance, setting the stage for well targeted analyses that extend theoretical models in important new directions. The FACHS sample is particularly valuable because a large body of evidence has accumulated that demonstrates that both genetic (G), gene-environment correlations (rGE) and gene-environment (GxE) interactions are important in influencing vulnerability to a wide variety health-related outcomes including obesity, hypertension and depression. To date, however, these studies have largely focused on populations of northern European ethnicity to the exclusion of other ethnic groups. In addition, the current sample provides an opportunity to examine previously unrecognized resilience factors in the AA population. We propose to identify specific risk and resilience factors for depression and substance. We hypothesize that G, rGE, and GxE interactions comprise a portion of the risk and resiliency factors responsible for altering vulnerability to depression and substance use in these women. To test this hypothesis we will 1) collect DNA samples from 1076 subjects (primary and secondary care givers with approximately 200 of the secondary care givers being marital partners), 2) conduct genotyping studies of the best validated candidate genes or loci, 3) conduct analyses of the resulting data to identify factors conveying risk or resilience to depression or substance use, and 4) then examine these factors in the context of longitudinal, contextually sensitive, developmental models of depression and substance use. As a direct result of these studies, we will determine specific G, rGE and GxE effects that either confer protection or confer increased risk for depression, substance use and other health related outcomes among AA women. The purpose of this grant application is to add a molecular genetics component to a currently funded study of the effects of behavioral and environmental factors on psychological well-being and diagnostic status of African-American (AA) subjects participating in the Family and Community Health Study (FACHS)
Keywords: 0-11 years old; 11 year old; 21+ years old; 5HT transporter; 5HTT protein; AOD use; Active Follow-up; Address; Adult; Adult Children; Adult Daughters; Adult Sons; Affect; African American; Afro American; Afroamerican; Aggregated Data; Aggregation, Data; Alcohol Drinking; Alcohol consumption; Alcohol or Other Drugs use; American; Anxiety; Applications Grants; Articulation; Attention; Behavior; Behavioral; Behavioral Genetics; Biocompatible Materials; Biological; Biomaterials; Black Populations; Black or African American; Blood; Blood Pressure, High; Blood Sample; Blood specimen; Candidate Disease Gene; Candidate Gene; Care Givers; Caregivers; Caring; Caucasian; Caucasian Race; Caucasians; Caucasoid; Caucasoid Race; Censuses; Characteristics; Child; Child Youth; Children (0-21); Cognitive; Collaborations; Collection; Communities; Companions; Complex; Consent; DNA; DSM-IV; DSM4; Data; Data Aggregation; Data Collection; Demographic Factors; Deoxyribonucleic Acid; Depression; Development; Diagnostic; Diagnostic and Statistical Manual of Mental Disorders, 4th edition; Diagnostic and Statistical Manual of Mental Disorders-IV; Disease; Disorder; Distress; Economic Income; Economical Income; Emergent Technologies; Emerging Technologies; Emotional well being; Environment; Environmental Factor; Environmental Risk Factor; Epigenetic; Epigenetic Change; Epigenetic Mechanism; Epigenetic Process; EtOH drinking; Ethnic Origin; Ethnic group; Ethnicity; Ethnicity aspects; European; Event; Exclusion; Family; Family and Community Health Study; Feels well; Female; Foundations; Funding; Future; Gene variant; Genes; Genetic; Genetic Determinants of Behavior; Genetic Diversity; Genetic Markers; Genetic Polymorphism; Genetic Predisposition; Genetic Predisposition to Disease; Genetic Susceptibility; Genetic Variation; Genetic analyses; Genetics, Behavioral; Genotype; Gibbons; Grant; Grant Proposals; Grants, Applications; Haplotypes; Head and Neck, Saliva; Health; History; Household; Human, Adult; Human, Child; Hylobates; Hylobates Genus; Hypertension; Income; Individual; Inherited Predisposition; Inherited Susceptibility; Institution; Interview; Investigation; Investigators; Iowa; Joints; Lead; Length of Life; Life; Life Cycle; Life Cycle Stages; Link; Literature; Longevity; Measures; Mediating; Mental Depression; Mental Health; Mental Hygiene; Mental well-being; Method LOINC Axis 6; Methodology; Methods; Minisatellite Repeats; Minisatellites; Modeling; Models, Theoretic; Molecular; Molecular Genetic; Molecular Genetics; NIMH; National Institute of Mental Health; National Institute of Mental Health (U.S.); Neighborhoods; Neuroses; Neurotic Disorders; Nicotine; Nomascus; Normal mental condition; Normal mental state; Normal psyche; Obesity; Occidental; Offspring, Adult; Outcome; Parents; Participant; Patient Self-Report; Pb element; Personality; Phase; Phenotype; Polymorphism (Genetics); Polymorphism, Genetic; Population; Population Study; Poverty; Prevention; Primary Care; Primary Health Care; Primary Healthcare; Principal Investigator; Procedures; Process; Psychological Health; Psychological Well Being; Psychologist; Psychoneuroses; Psychopathology; Psychosocial Assessment and Care; Psychosocial Factor; Pyridine, 3-(1-methyl-2-pyrrolidinyl)-, (S)-; Qualifying; R01 Mechanism; R01 Program; RPG; Recording of previous events; Recruitment Activity; Research; Research Grants; Research Personnel; Research Project Grants; Research Projects; Research Projects, R-Series; Research Resources; Researchers; Resources; Reticuloendothelial System, Blood; Risk; Role; SNP genotyping; Saliva; Sampling; Self-Report; Sense of well-being; Shapes; Simple Repetitive Sequence; Single-Parent Family; Source; Staging; Statistical Methods; Stratification; Stress; Structure; Substance Use Disorder; Survival Analyses; Survival Analysis; Symphalangus; Testing; Theoretical model; Thinking; Thinking, function; Time; United States National Institute of Mental Health; VNTR; VNTR Loci; VNTR Region; VNTR Sequences; Variable Number of Tandem Repeats; Variable Tandem Repeats; Variant; Variation; Variation (Genetics); Vascular Hypertensive Disease; Vascular Hypertensive Disorder; Well in self; Woman; Work; abnormal psychology; adiposity; adult human (21+); adult youth; alcohol ingestion; alcohol intake; alcohol product use; alcohol use; alcoholic beverage consumption; alcoholic drink intake; allelic variant; base; behavior genetics; black American; case control; children; corpulence; corpulency; corpulentia; disease/disorder; eleven year old; environment effect on gene; environmental risk; ethanol consumption; ethanol drinking; ethanol ingestion; ethanol intake; ethanol product use; ethanol use; etoh use; experience; family structure; follow-up; gene environment interaction; genetic analysis; genetic etiology; genetic mechanism of disease; genetic vulnerability; heavy metal Pb; heavy metal lead; hyperpiesia; hyperpiesis; hypertensive disease; inner city; innovate; innovation; innovative; insight; interest; life course; life span; lifespan; male; member; men; men`s; mid life; mid-life; middle age; middle aged; midlife; neurotic; neuroticism; obese; obese people; obese person; obese population; polymorphism; primary outcome; psychologic; psychological; psychological wellness; psychosocial; psychosocial assessment; psychosocial care; psychosocial studies; psychosocial support; psychosocial variables; public health relevance; racism; recruit; repository; resilience; response; rural area; self wellness; serotonin transporter; social role; sodium-dependent serotonin transporter; substance use; success; trait; translational study; white race; young adult; youngster
Project start date: 2008-07-01
Project end date: 2013-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-070
5R01MH080898-03 (2010): $592584
Grants awarded to Robert A Philibert
GENETIC STUDIES OF SUBSTANCE ABUSE IN IOWA ADOPTEES
Robert A Philibert
University Of Iowa, Iowa City, Ia 52242
Grant 5R01DA015789-05 from National Institute On Drug Abuse
Abstract: The purpose of this revised grant application is to solicit funding to add a molecular genetic component to the extensive epidemiologic data on Substance Use Disorders (SUD) available in the Iowa Adoption Studies. These epidemiologic studies include over 900 adult adoptees, separated at birth from biologic parents, interviewed over a 20 year period, who are now being re-interviewed with a focus upon lifetime substance use/abuse/dependency. Over the past two decades in studies of these adoptees, our research group has shown significant genetic and environmental effects and gene-environment interactions that affect both early life risk factors for substance abuse and the course of adult substance use/abuse/dependency. The adoption paradigm has furthered the study of the development of risk behaviors for SUD by allowing the examination of how genetic factors may interact with environmental factors such as parenting behaviors in the adoptive home and is the study design of choice for the detection of these important gene environment interactions. In this application, we hypothesize that genetic variability and certain gene environment interactions are responsible for increased vulnerability to SUD, and in particular, Nicotine, Alcohol and Marijuana abuse/dependence. To test this hypothesis we will 1) Conduct follow-up behavioral and cognitive assessments (including quantitative measures of SUD risk), then collect DNA samples from the our well characterized cohort of adoptees 2) conduct candidate and single nucleotide polymorphism analysis with respect to the best validated candidate genes or loci, and 3) analyze the resulting data using association and multifactorial regression to create a testable model of single gene, gene* gene, environmental and gene*environment contributions to the susceptibility to SUD. As direct result of these experiments, we will determine specific gene and gene-environment interactions that contribute to increased vulnerability to SUD. The identification of these interactions, and in particular gene x environment interactions, is important as it will allow the development of more effective biological and environmental (e.g. changing parenting behaviors or the formulation of new behavioral treatment strategies) interventions for the treatment of SUD. As an indirect result of these experiments, the scientific community will gain a unique and valuable genetic resource that can be utilized by other investigators of genetic and epidemiologic vulnerability to SUD in showing that these Iowa Adoption Studies through the NIDA Genetics Consortium
Keywords: 21+ years old; AD/HD; ADHD; AOD use; Accounting; Active Follow-up; Adoption; Adult; Affect; Alcohol or Other Drugs use; Alcohols; Algorithms; Applications Grants; Attention deficit hyperactivity disorder; Attention-Deficit Disorder, Predominantly Hyperactive-Impulsive Type; Behavior Conditioning Therapy; Behavior Modification; Behavior Therapy; Behavior Treatment; Behavior assessment; Behavior or Life Style Modifications; Behavioral; Behavioral Conditioning Therapy; Behavioral Genetics; Behavioral Modification; Behavioral Therapy; Behavioral Treatment; Biological; Birth; Blood Sample; Blood specimen; Candidate Disease Gene; Candidate Gene; Cell Line; Cell Lines, Strains; CellLine; Chemical Class, Alcohol; Cognitive; Collaborations; Communities; Conditioning Therapy; Conduct Disorder; Consensus; Coupled; DNA; Data; Deoxyribonucleic Acid; Dependence; Dependency; Dependency (Psychology); Detection; Development; Diagnostic; Disease regression; Doctor of Medicine; Doctor of Philosophy; Drug Formulations; Environment; Environmental Factor; Environmental Risk Factor; Epidemiologic Research; Epidemiologic Studies; Epidemiological Studies; Epidemiology Research; Female; Formulation; Formulations, Drug; Funding; Genes; Genetic; Genetic Determinants of Behavior; Genetics, Behavioral; Genotype; Grant Proposals; Grants, Applications; Haplotypes; History; Home; Home environment; Human, Adult; Hyperactivity Disorder NOS; Hyperactivity Disorder, Predominantly Hyperactive-Impulsive Type; Hyperkinetic Syndrome; Individual; Institution; Intervention; Intervention Strategies; Interview; Investigators; Iowa; Lead; Life; Life Style Modification; Longitudinal Studies; M.D.; Marijuana Abuse; Measures; Mediator; Mediator of Activation; Mediator of activation protein; Minisatellite Repeats; Minisatellites; Modeling; Molecular; Molecular Genetic; Molecular Genetics; NIDA; National Institute of Drug Abuse; Nicotine; Parenting; Parenting behavior; Parents; Parturition; Pathogenesis; Pb element; Personal Satisfaction; Ph.D.; PhD; Phase; Phenotype; Polymorphism Analysis; Polymorphism Detection; Polymorphism, Single Base; Population; Predisposition; Principal Investigator; Purpose; Pyridine, 3-(1-methyl-2-pyrrolidinyl)-, (S)-; Qualifying; Rate; Recording of previous events; Regression; Research; Research Design; Research Personnel; Research Training; Researchers; Risk; Risk Behaviors; Risk Factors; Risky Behavior; Role; SNP; SNP genotyping; SNPs; Sampling; Simple Repetitive Sequence; Single Nucleotide Polymorphism; Study Type; Substance Use Disorder; Substance abuse problem; Survival Analyses; Survival Analysis; Susceptibility; Symptoms; Testing; Update; VNTR; VNTR Loci; VNTR Region; VNTR Sequences; Variable Number of Tandem Repeats; Variable Tandem Repeats; abuse of substances; adult human (21+); at risk behavior; attention deficit hyperactive disorder; base; behavior genetics; behavior intervention; behavioral assessment; behavioral intervention; cohort; cultured cell line; disease risk; disorder risk; emotional dependency; environment effect on gene; environmental risk; experience; experiment; experimental research; experimental study; follow-up; gene environment interaction; genetic resource; heavy metal Pb; heavy metal lead; immortalized cell; improved; innovate; innovation; innovative; interventional strategy; long-term study; male; proband; psychosocial; repository; research study; size; social role; study design; substance abuse; substance use; well-being
Project start date: 2004-07-01
Project end date: 2010-06-30
Budget start date: 1-JUL-2008
Budget end date: 30-JUN-2010
PFA/PA: PA-00-115
5R01DA015789-05 (2008): $0
5R01DA015789-04 (2007): $717623
5R01DA015789-03 (2006): $714089
5R01DA015789-02 (2005): $815034
1R01DA015789-01A2 (2004): $784196
A Thyroid Receptor Co-activator Hypothesis For Psychosis
Robert A Philibert
University Of Iowa Iowa City, Ia 52242
Grant 5K08MH064714-04 from National Institute Of Mental Health IRG: ZRG1
Abstract: Schizophrenia is a neurodevelopmental syndrome that affects approximately 1 percent of the U.S. population and is characterized by the presence of hallucinations and delusions. Genetic factors are thought to account for the majority of the vulnerability to illness for this syndrome. These genetic factors are thought to be composed of major, moderate ant mild effect loci. The identification and characterization of genetic factors of even mild effect loci is a critical step in the process of understanding the pathogenesis of this group of disorders. In prior moleular studies, the candidate has identified an exonic polymorphism (HOPA12bP) in a critical portion of a gene for a thyroid receptor co-activator named HOPAthat is associated with a behavioral endophenotype that include schizophrenia and hypothyroidism. In this five year training grant, the candidate proposes to focus on the behavioral syndrome that is associated with the polymorphism and 1) demonstrate segregation of the polymorphism with illness. 2 refine the phenotype associated with the polymorphism, and 3) identify other mutations that may be related to illness. Scientific Aims of this grant are 1). Peform case control analyses on schizophrenic probands with the HOPA12bp polymorphism. Schizophrenic HOPA probands will be identified and compared to matched case controls for cognitive/behavioral, endocrinological and medical differences. 2. Conduct a focused linkage study of the families of HOPA12bp probands. Structured interviews will be used to assess the presence of cognitive/behavioral and medical co-morbidity in the first-degree relatives of control and HOPA12bP probands. These results will be correlated with genetic status. 3). Conduct SSCP analysis across the HOPA Gene to detect other potentially pathogenic mutations. Mutation analysis will be performed using DNA from other schizophrenic patients to detect other mutations in theHOPA gene that can result in result in this syndrome or related phenotypes. Training Aims of this grant are to 1) develop clinical skills in the diagnosis and standardized measurement of complex behavior and endocrinological disorders, and 2) learn medical and psychiatric epidemiology, ethics, and biostatistical approaches to complex disorders. The net effect will be to produce an independent investigator capable of functional and translational research.
Keywords: behavioral genetics, genetic polymorphism, hypothyroidism, linkage mapping, receptor expression, schizophrenia, thyroid gland, family genetics, genetic transcription, human subject, interview, patient oriented research, single strand conformation polymorphism
Project start date: 2002-01-01
Project end date: 2005-12-31
5K08MH064714-04 (2005): $171555
5K08MH064714-03 (2004): $171555
5K08MH064714-02 (2003): $171555