Genetic overlap between Alzheimer’s disease and Parkinson’s disease at the MAPT locus

• DOI: 10.1038/mp.2015.6
• Publication Date: 2015-02-17T08:55:03Z
• Authors: R S Desikan; A J Schork; Y Wang; A Witoelar; M Sharma; L K McEvoy; D Holland; J B Brewer; C-H Chen; W K Thompson; D Harold; J Williams; M J Owen; M C O'Donovan; M A Pericak-Vance; R Mayeux; J L Haines; L A Farrer; G D Schellenberg; P Heutink; A B Singleton; A Brice; N W Wood; J Hardy; M Martinez; S H Choi; A DeStefano; M A Ikram; J C Bis; A Smith; A L Fitzpatrick; L Launer; C van Duijn; S Seshadri; I D Ulstein; D Aarsland; T Fladby; S Djurovic; B T Hyman; J Snaedal; H Stefansson; K Stefansson; T Gasser; O A Andreassen; A M Dale
• Keywords: Male; Aging; Biological Psychology; Clinical sciences; genetics [Alzheimer Disease]; Neurodegenerative; Alzheimer's Disease; Medical and Health Sciences; Clinical and health psychology; 0302 clinical medicine; pathology [Brain]; genetics [Parkinson Disease]; 80 and over; ADNI; Psychology; 2.1 Biological and endogenous factors; Aetiology; Psychiatry; Aged, 80 and over; Parkinson's Disease; Clinical and Health Psychology; Brain; Genetic Pleiotropy; Parkinson Disease; Single Nucleotide; Biological Sciences; Middle Aged; 3. Good health; Neurological; ADGC; Female; Human; EMC COEUR-09; EMC NIHES-01-64-01; Clinical Sciences; MAPT protein, human; tau Proteins; Polymorphism, Single Nucleotide; Chromosomes; Article; 03 medical and health sciences; Apolipoproteins E; Alzheimer Disease; Genetics; Acquired Cognitive Impairment; CHARGE and IPDGC Investigators; Humans; GERAD; ddc:610; Polymorphism; Alleles; Aged; Biomedical and Clinical Sciences; Prevention; Pair 17; Human Genome; Psychology and Cognitive Sciences; Neurosciences; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); Brain Disorders; genetics [tau Proteins]; Genetic Loci; Biological psychology; genetics [Apolipoproteins E]; Dementia; Chromosomes, Human, Pair 17; Genome-Wide Association Study

We investigated the genetic overlap between Alzheimer's disease (AD) and Parkinson's disease (PD). Using summary statistics (P-values) from large recent genome-wide association studies (GWAS) (total n=89 904 individuals), we sought to identify single nucleotide polymorphisms (SNPs) associating with both AD and PD. We found and replicated association of both AD and PD with the A allele of rs393152 within the extended MAPT region on chromosome 17 (meta analysis P-value across five independent AD cohorts=1.65 × 10(-7)). In independent datasets, we found a dose-dependent effect of the A allele of rs393152 on intra-cerebral MAPT transcript levels and volume loss within the entorhinal cortex and hippocampus. Our findings identify the tau-associated MAPT locus as a site of genetic overlap between AD and PD, and extending prior work, we show that the MAPT region increases risk of Alzheimer's neurodegeneration.