Parkinson disease (PD) affects over one million people in the United States alone. PD is a complex disorder, with both genetic and environmental factors contributing to susceptibility. Dissecting the etiology of complex diseases, such as PD, requires the integration of many different laboratory and statistical approaches. This project seeks to continue funding to search for genes contributing to idiopathic PD. Recognizing the complex etiology of PD and the difficulties in uncovering genes involved in complex diseases, we have adopted the approach of """"""""genomic convergence"""""""". We have relied on the convergence of evidence from genetic linkage studies, expression studies and family-based association analysis to yield strong candidates for PD susceptibility genes. Through this proposal, we will continue to examine candidate genes based on the principle of genomic convergence. We will enhance these efforts by including analysis of complex genetic and environmental interactions, as well as developing methods to reduce heterogeneity in our large family sample.
The specific aims of this proposal are: 1) Test biological candidate genes for association with PD; and candidates suggested by the genomic convergence of gene expression from project II and linkage analysis 2) Test for gene-gene interaction between candidate genes in PD; and 3) Test for gene-environment interaction between candidate genes and potential environmental risk factors for PD. This comprehensive analytic approach, guided by the expression analysis conducted in Project II and association mapping in Project IV of this proposal, will allow us to systematically evaluate and identify genes playing a role in PD.
|Petyuk, Vladislav A; Chang, Rui; Ramirez-Restrepo, Manuel et al. (2018) The human brainome: network analysis identifies HSPA2 as a novel Alzheimer’s disease target. Brain 141:2721-2739|
|Sims, Rebecca (see original citation for additional authors) (2017) Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease. Nat Genet 49:1373-1384|
|Jun, Gyungah R; Chung, Jaeyoon; Mez, Jesse et al. (2017) Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimers Dement 13:727-738|
|Nuytemans, Karen; Maldonado, Lizmarie; Ali, Aleena et al. (2016) Overlap between Parkinson disease and Alzheimer disease in ABCA7 functional variants. Neurol Genet 2:e44|
|Karch, Celeste M; Ezerskiy, Lubov A; Bertelsen, Sarah et al. (2016) Alzheimer's Disease Risk Polymorphisms Regulate Gene Expression in the ZCWPW1 and the CELF1 Loci. PLoS One 11:e0148717|
|Mez, Jesse; Mukherjee, Shubhabrata; Thornton, Timothy et al. (2016) The executive prominent/memory prominent spectrum in Alzheimer's disease is highly heritable. Neurobiol Aging 41:115-121|
|Ridge, Perry G; Hoyt, Kaitlyn B; Boehme, Kevin et al. (2016) Assessment of the genetic variance of late-onset Alzheimer's disease. Neurobiol Aging 41:200.e13-200.e20|
|Hohman, Timothy J; Bush, William S; Jiang, Lan et al. (2016) Discovery of gene-gene interactions across multiple independent data sets of late onset Alzheimer disease from the Alzheimer Disease Genetics Consortium. Neurobiol Aging 38:141-150|
|Jun, G; Ibrahim-Verbaas, C A; Vronskaya, M et al. (2016) A novel Alzheimer disease locus located near the gene encoding tau protein. Mol Psychiatry 21:108-17|
|Ebbert, Mark T W; Boehme, Kevin L; Wadsworth, Mark E et al. (2016) Interaction between variants in CLU and MS4A4E modulates Alzheimer's disease risk. Alzheimers Dement 12:121-129|
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