goate_alison

Alison Goate, DPhil

Samuel & Mae S Ludwig Professor of Genetics in Psychiatry

Genetic and genomic approaches to uncovering susceptibility to neurological and psychiatric diseases Read More

Email: goatea@psychiatry.wustl.edu
Lab Phone: (314) 362-8691
Website: Goate Lab
Lab Location: BJC Institute of Health 9202
Keywords: genetics of Alzheimer's disease and other tauopathies, frontotemporal dementia, next generation sequencing, biomarkers, endophenotypes, Genome-wide association studies, functional studies

Genetic and genomic approaches to uncovering susceptibility to neurological and psychiatric diseases

Kauwe et al. (2007) Annals of Neurology

 

The principal focus of the laboratory is the molecular genetics of neuropsychiatric diseases. The two major research areas are Alzheimer’s disease and substance dependence. We are using genetic (GWAS) and genomic (sequencing) strategies to identify rare and common alleles predisposing to these disorders. Our AD studies have recently focused on the use of cerebrospinal fluid biomarker levels such as A-beta and tau as quantitative traits in genetic analyses. These studies have demonstrated in humans that APOE influences risk for AD by an A-beta dependent mechanism. We have also demonstrated that two genes, which influence CSF tau levels, affect the rate of progression of AD but not risk for disease. GWAS using both of these phenotypes are ongoing and will complement our GWAS in case control datasets. A second project focused on rare variation has screened the proband from 450 densely affected late onset AD families for variation in the known dementia causing genes. This work has shown that at least 5% of these families have disease caused by mutations in genes previously associated with early onset disease. The largest families without pathogenic mutations will be used for whole exome sequencing for novel disease genes.

GWAS in nicotine dependence case control datasets has provided compelling evidence for the role of common risk variants in several nicotinic receptor sub-unit genes and in the major nicotine metabolism enzyme (CYP2A6). We are performing additional studies to determine the functional variants and the potential mechanism of risk. We have also undertaken sequencing studies to identify rare variation in the nicotinic receptor genes that might explain additional genetic variance. Our alcohol dependence study is a family based study. We are currently performing a GWAS in these families and have recently begun whole exome sequencing in a very large family with evidence for a single major locus influencing risk for alcohol dependence.

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