Eating Disorders and Parkinson's Disease - 2: Population Burden, Genetic Epidemiology and Shared Genomics

饮食失调与帕金森病——2:人群负担、遗传流行病学和共享基因组学

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Abstract

OBJECTIVE: We reviewed the epidemiologic and genomic literature and performed genomic analyses to identify population burdens (Eating Disorders, ED and Parkinson's Disease, PD) and shared genetic risk (Anorexia Nervosa, AN and PD), after we previously demonstrated two-to four-fold relative risks of a family history of Parkinson's Disease in families of individuals with ED. METHOD: We reviewed the epidemiology of both disorders and published genome-wide association studies (GWAS), searched PD GWAS findings with AN associated genome-wide significant SNPs and associated genes and regions, and performed conditional/conjunctional false discovery rate genomic analyses of AN and PD summary statistics to identify shared genetics. RESULTS: The global population burden of ED and PD are similar despite differences in age of onset and sex ratio. GWAS review and linkage disequilibrium analysis showed that genome-wide significant variants from AN GWAS and PD GWAS in the chr3p21.31 region are correlated. We identified a chr3p21.31 variant with joint association with both disorders; this variant has functional linkages to 40 genes. CONCLUSIONS: ED and PD share neuropsychological, neurobiological, and genetic risk factors, including association with the complex chr3p21.31 locus. Translational analyses leveraging disorder-specific research resources may benefit our understanding of the genetics and neuropsychiatric mechanisms of both disorders.

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