Replication of GWAS associations for GAK and MAPT in Parkinson's disease.
In the investigation of disease aetiology, the genome-wide association study (GWAS) provides a hypothesis-free investigation of the broader human genome and, as with all scientific investigations, replication is essential to validate any findings. To date, six GWAS have been performed to investigate the influence of common genetic variation in Parkinson's disease (PD) and only two associations have been replicated: alpha synuclein (SNCA) and microtubule-associated protein tau (MAPT), both PD candidate genes before GWAS. In our population-based study, we genotyped four of the top single-nucleotide polymorphisms (SNPs) from a previous study. By using the identical analytic method and genetic model in our independent sample, we provide evidence for replication of rs1724425 near MAPT (OR = 0.74, P= 0.0163) and rs1564282 in cyclin G-associated kinase (GAK; OR = 1.61, P= 0.0151); rs3775478 of multimerin 1 (MMRN1) (P= 0.30) and rs356229 of SNCA (P= 0.14) did not replicate in our study population. While MAPT has been considered a PD candidate gene and has been observed in association with PD in other GWAS, GAK is a new candidate for investigation in future studies.
Department of Epidemiology, UCLA School of Public Health, Los Angeles, CA 90095-1772, USA. shannon.rhodes@ucla.edu
Shannon L
SL
Rhodes
Janet S
JS
Sinsheimer
Yvette
Y
Bordelon
Jeff M
JM
Bronstein
Beate
B
Ritz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015203:Reproducibility of Results; D051844:alpha-Synuclein / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
D047908:Intracellular Signaling Peptides and Proteins; C054369:MAPT protein, human; C497604:SNCA protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C486325:GAK protein, human; D017346:Protein Serine-Threonine Kinases