Research

IBG is one of the top facilities in the world for genetic research on behavior. Data collection and analysis are ongoing for several internationally renowned studies including the Colorado Adoption Project, the Colorado Twin Registry, the National Youth Survey Family Study, the Colorado Learning Disabilities Research Center, and the National Longitudinal Study of Adolescent Health. IBG is home to one of the nation's largest DNA repositories for research on human behavior, as well as housing a wide array of behaviorally and genetically defined lines of selected, recombinant inbred, transgenic, and knockout-gene mice.

Throughout its history IBG has been characterized by the breadth of its interdisciplinary research and training programs. Although the methodology of behavioral genetics is generally applicable to the study of individual differences for any characteristic, research at IBG is focused on behaviors of societal relevance.

Current research includes studies of aging, neurodegenerative disease, psychopathology, reading and learning disabilities, cognition, substance abuse, behavioral development, and evolution.

Societal Impact

Research Highlights

Reading Disability: demonstrated the genetic influence on reading difficulties (DeFries et al., 1987, Nature, 329: 537-539) and identified a locus on chromosome 6p which contributes to this genetic risk (Cardon et al, 1994, Science, 266: 267-269; Fisher & DeFries, 2002, Nature Reviews Neuroscience, 3, 767-780).

Aging: discovered a mutation, age-1, that results in a two-fold increase in the life span of the nematode, C. elegans, a model organism for biological research (Johnson TE, Science, 1990, 249: 908-912). Developed the only existing method for predicting subsequent life span (Rea et al., 2005, Nature Genetics, 37:894-898).

Nicotinic receptors: characterized the molecular biology of nicotinic receptors and the behavioral consequences of their genetic variation in animal models, and demonstrated that activation of one of these receptors is important in the development of nicotine dependence (Tapper et al, 2004, Science, 306: 1029-1032). Genetic variation in these nicotinic receptors has been associated with drug seeking behaviors in our human study populations (Schlaepfer et al, 2008. Current Drug Abuse Reviews, 1:124-134).

Risky behavior: described a heritable trait, behavioral disinhibition, that predisposes individuals to a range of risky behaviors such as substance use and abuse, conduct problems, and impulsive behavior (Young et al, 2009, Journal of Abnormal Psychology, 102:78-87). Ongoing twin, adoption, and family studies include brain imaging and genome wide association studies to locate specific brain regions and genes associated with behavioral disinhibition.

Personality: identified chromosomal loci influencing anxiety in a mouse model of neuroticism (Flint et al, 1995, Science, 269: 1432-1435).

Cognition: demonstrated that executive cognitive control, associated with frontal cortical function, is genetically influenced independently of general intelligence (Friedman et al, 2008, Journal of Experimental Psychology: General, 137: 201-225).

Genetics of complex traits: Using single nucleotide polymorphism data on a large (N=22,000) case-control dataset, we showed that autozygosity (a genetic signature of distant inbreeding) increases the risk of schizophrenia (Keller, M. C., Simonson, M. A., Ripke, S., Neale, B. M., Gejman, P. V., Howrigan, D. P., Lee, S. H., Lencz, T., Levinson, D. F., Sullivan, P. F., & the Schizophrenia Psychiatric Genome- Wide Association Study (GWAS) Consortium (2012). Runs of homozygosity implicate autozygosity as a schizophrenia risk factor. PLoS Genetics, 8, e1002656 ). This suggests that alleles that predispose to schizophrenia have tended to be deleterious over evolutionary time. Using the same dataset, we also showed that about 1/3 of the total additive genetic variation in risk to schizophrenia is tagged by common SNPs (Lee, S. H., DeCandia, T., Ripke, S., Yang, J., The Schizophrenia Psychiatric Gemone-Wide Association Study Consortium (PGC-SZ), The International Schizophrenia Consortium (ISC), The Molecular Genetics of Schizophrenia Collaboration (MGS), Sullivan, P. F., Goddard, M. E., Keller, M. C.†, Visscher, P. M. †, Wray, N. R.† (2012). Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nature Genetics, 44, 247-250.(†joint senior author)).