Human Genetics

, Volume 124, Issue 6, pp 593–605

Genomewide association study for susceptibility genes contributing to familial Parkinson disease

  • Nathan Pankratz
  • Jemma B. Wilk
  • Jeanne C. Latourelle
  • Anita L. DeStefano
  • Cheryl Halter
  • Elizabeth W. Pugh
  • Kimberly F. Doheny
  • James F. Gusella
  • William C. Nichols
  • Tatiana Foroud
  • Richard H. Myers
  • The PSG—PROGENI and GenePD Investigators, Coordinators and Molecular Genetic Laboratories
Original Investigations

DOI: 10.1007/s00439-008-0582-9

Cite this article as:
Pankratz, N., Wilk, J.B., Latourelle, J.C. et al. Hum Genet (2009) 124: 593. doi:10.1007/s00439-008-0582-9

Abstract

Five genes have been identified that contribute to Mendelian forms of Parkinson disease (PD); however, mutations have been found in fewer than 5% of patients, suggesting that additional genes contribute to disease risk. Unlike previous studies that focused primarily on sporadic PD, we have performed the first genomewide association study (GWAS) in familial PD. Genotyping was performed with the Illumina HumanCNV370Duo array in 857 familial PD cases and 867 controls. A logistic model was employed to test for association under additive and recessive modes of inheritance after adjusting for gender and age. No result met genomewide significance based on a conservative Bonferroni correction. The strongest association result was with SNPs in the GAK/DGKQ region on chromosome 4 (additive model: p = 3.4 × 10−6; OR = 1.69). Consistent evidence of association was also observed to the chromosomal regions containing SNCA (additive model: p = 5.5 × 10−5; OR = 1.35) and MAPT (recessive model: p = 2.0 × 10−5; OR = 0.56). Both of these genes have been implicated previously in PD susceptibility; however, neither was identified in previous GWAS studies of PD. Meta-analysis was performed using data from a previous case–control GWAS, and yielded improved p values for several regions, including GAK/DGKQ (additive model: p = 2.5 × 10−7) and the MAPT region (recessive model: p = 9.8 × 10−6; additive model: p = 4.8 × 10−5). These data suggest the identification of new susceptibility alleles for PD in the GAK/DGKQ region, and also provide further support for the role of SNCA and MAPT in PD susceptibility.

Supplementary material

439_2008_582_MOESM1_ESM.doc (111 kb)
Supplementary material (DOC 111 kb)

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Nathan Pankratz
    • 1
  • Jemma B. Wilk
    • 2
  • Jeanne C. Latourelle
    • 2
  • Anita L. DeStefano
    • 2
    • 3
  • Cheryl Halter
    • 1
  • Elizabeth W. Pugh
    • 4
  • Kimberly F. Doheny
    • 4
  • James F. Gusella
    • 5
  • William C. Nichols
    • 6
  • Tatiana Foroud
    • 1
  • Richard H. Myers
    • 2
  • The PSG—PROGENI and GenePD Investigators, Coordinators and Molecular Genetic Laboratories
  1. 1.Indiana University School of MedicineIndianapolisUSA
  2. 2.Department of NeurologyBoston University School of MedicineBostonUSA
  3. 3.Boston University School of Public HealthBostonUSA
  4. 4.Johns Hopkins University School of MedicineBaltimoreUSA
  5. 5.Massachusetts General Hospital and Harvard Medical SchoolBostonUSA
  6. 6.Cincinnati Children’s Hospital Medical CenterCincinnatiUSA