TY - JOUR
T1 - Fine-mapping and candidate gene investigation within the PARK10 locus
AU - Haugarvoll, Kristoffer
AU - Toft, Mathias
AU - Skipper, Lisa
AU - Heckman, Michael G.
AU - Crook, Julia E.
AU - Soto, Alexandra
AU - Ross, Owen A.
AU - Hulihan, Mary M.
AU - Kachergus, Jennifer M.
AU - Sando, Sigrid B.
AU - White, Linda R.
AU - Lynch, Timothy
AU - Gibson, J. Mark
AU - Uitti, Ryan J.
AU - Wszolek, Zbigniew K.
AU - Aasly, Jan O.
AU - Farrer, Matthew J.
N1 - Funding Information:
We gratefully thank the patients, families and controls for their participation in this study. Mayo Clinic Jacksonville is a MK Udall Parkinson’s Disease Research Center of Excellence (NINDS P01 NS40256) and we thank all collaborators of the Udall Center. This study was also supported by the National Institutes of Health (R01 AG022579), the Research Council of Norway (Grant no. 153487/ V50) and Reberg’s Legacy (JOA).
PY - 2009
Y1 - 2009
N2 - Herein, we investigate whether single-nucleotide polymorphisms (SNPs) across the PARK10 locus are associated with susceptibility to Parkinson's disease (PD) or age at onset (AAO) of disease. One hundred and eighty-eight SNPs were genotyped across the PARK10 locus in 180 PD patients and 180 controls from central Norway (stage 1). We then used the linkage disequilibrium (LD) structure from stage 1 to select 75 SNPs for genotyping in 186 patients and 186 controls from Ireland (stage 2). Nineteen SNPs were selected from this and previous studies for follow-up in an extended Norwegian series (530 patients and 1142 controls), the Irish series and a US series (221 patients and 221 controls) (stage 3). After correction for multiple testing, markers within ubiquitin specific peptidase 24 (USP24) are significantly associated with PD within Norwegian, Irish, and US series combined (rs13312: odds ratio (OR) 0.78, P<0.001; rs487230: OR 0.80, P=0.001). Independently, the association for rs13312 is strongest in the extended Norwegian series (OR 0.76, P=0.005), although not significant after correction for multiple testing (P≤0.003 is considered significant). ORs in the Irish series are almost identical, and a similar but a weaker effect was observed for the US series. No marker showed consistent association with AAO. Our data indicate that genetic variability in USP24 is associated with PD. Although our work extends and confirms a previous report, the observed effect size does not explain the PARK10 linkage peak.
AB - Herein, we investigate whether single-nucleotide polymorphisms (SNPs) across the PARK10 locus are associated with susceptibility to Parkinson's disease (PD) or age at onset (AAO) of disease. One hundred and eighty-eight SNPs were genotyped across the PARK10 locus in 180 PD patients and 180 controls from central Norway (stage 1). We then used the linkage disequilibrium (LD) structure from stage 1 to select 75 SNPs for genotyping in 186 patients and 186 controls from Ireland (stage 2). Nineteen SNPs were selected from this and previous studies for follow-up in an extended Norwegian series (530 patients and 1142 controls), the Irish series and a US series (221 patients and 221 controls) (stage 3). After correction for multiple testing, markers within ubiquitin specific peptidase 24 (USP24) are significantly associated with PD within Norwegian, Irish, and US series combined (rs13312: odds ratio (OR) 0.78, P<0.001; rs487230: OR 0.80, P=0.001). Independently, the association for rs13312 is strongest in the extended Norwegian series (OR 0.76, P=0.005), although not significant after correction for multiple testing (P≤0.003 is considered significant). ORs in the Irish series are almost identical, and a similar but a weaker effect was observed for the US series. No marker showed consistent association with AAO. Our data indicate that genetic variability in USP24 is associated with PD. Although our work extends and confirms a previous report, the observed effect size does not explain the PARK10 linkage peak.
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U2 - 10.1038/ejhg.2008.187
DO - 10.1038/ejhg.2008.187
M3 - Article
C2 - 18854859
AN - SCOPUS:60749108349
SN - 1018-4813
VL - 17
SP - 336
EP - 343
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 3
ER -