A.B., Biology, The University of Chicago, 1992
Fax: (773) 834-0505
Genetic variation contributes to individual differences in the risk for a variety of psychiatric and other common diseases. For the common psychiatric diseases, multiple genes work in concert to confer risk, and interact with one another, as well as the environment, to produce the observed phenotype. Identifying these genes, as well as understanding their complex interactions, promises to revolutionize the diagnosis and treatment of psychiatric diseases. Our research uses mice as a model genetic system to identify specific genes that contribute to heritable disorders
Genetic determinants of sensitivity to methamphetamine (MA) in mice and humans. Individual differences in the sensitivity to drugs of abuse are controlled by both genetic and environmental factors. The genetic variants associated with differential sensitivity to abused drugs may partially underlie genetic liability for drug abuse. We have integrated QTL mapping with gene expression analysis and used these two approaches to identify genes that are associated with differential sensitivity to MA. Preliminary work with Harriet de Wit (Psychiatry) has established that at least one of these genes also regulates sensitivity to MA in human subjects who were administered MA in a controlled laboratory setting.
Translational genetic approach to fear and anxiety. Fear learning and anxiety disorders may be regulated by common genetic substrates. We selectively bred mice for high or low levels of fear learning to identify both QTLs for fear learning and gene-expression differences between the high and low selected lines. We have also shown that selection altered other aspects of fear and anxiety-like behavior. Candidate genes identified by this approach will be screened against several large human samples that have been phenotyped for fear and anxiety related traits.
Candidate gene studies of a promising intermediate phenotype: failure to replicate.
(Apr 2013) Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 38(5):802-16 PMID:23303064
A simulation study of permutation, bootstrap, and gene dropping for assessing statistical significance in the case of unequal relatedness.
Psychopharmacology of theobromine in healthy volunteers.
(Feb 2013) Psychopharmacology PMID:23420115
Does COMT genotype influence the effects of d-amphetamine on executive functioning?
Glyoxalase 1 and its substrate methylglyoxal are novel regulators of seizure susceptibility.
(Feb 2013) Epilepsia PMID:23409935
Congenic dissection of a major QTL for methamphetamine sensitivity implicates epistasis.
(Jul 2012) Genes, brain, and behavior 11(5):623-32 PMID:22487465
Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal.
QTLs for murine red blood cell parameters in LG/J and SM/J F(2) and advanced intercross lines.
Translational genetic approaches to substance use disorders: bridging the gap between mice and humans.
Genome-wide association for fear conditioning in an advanced intercross mouse line.
Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids.
High-resolution genetic mapping using the Mouse Diversity outbred population.
Pavlovian fear memory circuits and phenotype models of PTSD.
(Feb 2012) Neuropharmacology 62(2):638-46 PMID:21782833
Genome-wide association for methamphetamine sensitivity in an advanced intercross mouse line.
Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).
Role of Glyoxalase 1 (Glo1) and methylglyoxal (MG) in behavior: recent advances and mechanistic insights.
Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line.
Assessment of behaviors modeling aspects of schizophrenia in Csmd1 mutant mice.
Mapping a mouse limbic seizure susceptibility locus on chromosome 10.
Genetic determinants for intramuscular fat content and water-holding capacity in mice selected for high muscle mass.
Fine-mapping alleles for body weight in LG/J × SM/J F₂ and F(34) advanced intercross lines.
Genetic analysis in the Collaborative Cross breeding population.
Anxiety and fear in a cross of C57BL/6J and DBA/2J mice: mapping overlapping and independent QTL for related traits.
(Jul 2011) Genes, brain, and behavior 10(5):604-14 PMID:21554534
Casein kinase 1 enables nucleus accumbens amphetamine-induced locomotion by regulating AMPA receptor phosphorylation.
OPRM1 gene variants modulate amphetamine-induced euphoria in humans.
Distinct genetic regions modify specific muscle groups in muscular dystrophy.
Dark matter: are mice the solution to missing heritability?
QTL Analysis of Type I and Type IIA Fibers in Soleus Muscle in a Cross between LG/J and SM/J Mouse Strains.
QTLRel: an R package for genome-wide association studies in which relatedness is a concern.
Modulation ofTcf7l2 expression alters behavior in mice.
Animal Models of Prenatal Protein Malnutrition Relevant for Schizophrenia(Patterson, Paul, Brown, Alan, Eds.)
Role of Genetics in Caffeine Response and Its Implications for Health
(2010) 211:245. Psychopharmacology (PDF)
More on ADORA.
(Dec 2010) Psychopharmacology 212(4):699-700 PMID:20802997
Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F(2) and advanced intercross lines.
(Oct 2010) Genes, brain, and behavior 9(7):759-67 PMID:20597988
Fine-mapping of muscle weight QTL in LG/J and SM/J intercrosses.
Genetics of caffeine consumption and responses to caffeine.
(Aug 2010) Psychopharmacology 211(3):245-57 PMID:20532872
Genome-wide association studies and the problem of relatedness among advanced intercross lines and other highly recombinant populations.
Catechol-O-methyltransferase val158met genotype modulates sustained attention in both the drug-free state and in response to amphetamine.
Differences in aggressive behavior and DNA copy number variants between BALB/cJ and BALB/cByJ substrains.
(Mar 2010) Behavior genetics 40(2):201-10 PMID:20033273
Polymorphisms in dopamine transporter (SLC6A3) are associated with stimulant effects of D-amphetamine: an exploratory pharmacogenetic study using healthy volunteers.
(Mar 2010) Behavior genetics 40(2):255-61 PMID:20091113
Are attention lapses related to d-amphetamine liking?
(Feb 2010) Psychopharmacology 208(2):201-9 PMID:19936714
More aroused, less fatigued: fatty acid amide hydrolase gene polymorphisms influence acute response to amphetamine.
Murine Warriors or Worriers: The Saga of Comt1, B2 SINE Elements, and the Future of Translational Genetics.