English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Lack of replication of the GRIN2A-by-coffee interaction in Parkinson disease

MPS-Authors
/persons/resource/persons50411

Lill,  Christina M.
Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50098

Bertram,  Lars
Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society;

External Resource
No external resources are shared
Fulltext (public)

Ahmed.pdf
(Publisher version), 226KB

Supplementary Material (public)
There is no public supplementary material available
Citation

Ahmed, I., Lee, P.-C., Lill, C. M., Nielsen, S. S., Artaud, F., Gallagher, L. G., et al. (2014). Lack of replication of the GRIN2A-by-coffee interaction in Parkinson disease. PLoS Genetics, 10(11): e1004788. doi:10.1371/journal.pgen.1004788.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0026-AFE2-9
Abstract
The etiology of Parkinson disease (PD) involves both genetic susceptibility and environmental exposures. In particular, coffee consumption is inversely associated with PD but the mechanisms underlying this intriguing association are unknown. According to a recent genome-wide gene–environment interaction study, the inverse coffee–PD association was two times stronger among carriers of the T allele of SNP rs4998386 in gene GRIN2A than in homozygotes for the C allele. We attempted to replicate this result in a similarly sized pooled analysis of 2,289 cases and 2,809 controls from four independent studies (Denmark, France, Seattle-United States (US), and Rochester-US) with detailed caffeinated coffee consumption data and rs4998386 genotypes. Using a variety of definitions of coffee drinking and statistical modeling techniques, we failed to replicate this interaction. Notably, whereas in the original study there was an association between rs4998386 and coffee consumption among controls, but not among cases, none of the datasets analyzed here indicated an association between rs4998386 and coffee consumption among controls. Based on large, well-characterized datasets independent from the original study, our results are not in favor of an interaction between caffeinated coffee consumption and rs4998386 for PD risk and suggest that the original finding may have been driven by an association of coffee consumption with rs4998386 in controls. The next years will likely see an increasing number of papers examining gene–environment interactions at the genome-wide level, which poses important methodological challenges. Our findings underline the need for a careful assessment of the findings of such studies.