IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0046199.html
   My bibliography  Save this article

Evaluation of Parkinson Disease Risk Variants as Expression-QTLs

Author

Listed:
  • Jeanne C Latourelle
  • Alexandra Dumitriu
  • Tiffany C Hadzi
  • Thomas G Beach
  • Richard H Myers

Abstract

The recent Parkinson Disease GWAS Consortium meta-analysis and replication study reports association at several previously confirmed risk loci SNCA, MAPT, GAK/DGKQ, and HLA and identified a novel risk locus at RIT2. To further explore functional consequences of these associations, we investigated modification of gene expression in prefrontal cortex brain samples of pathologically confirmed PD cases (N = 26) and controls (N = 24) by 67 associated SNPs in these 5 loci. Association between the eSNPs and expression was evaluated using a 2-degrees of freedom test of both association and difference in association between cases and controls, adjusted for relevant covariates. SNPs at each of the 5 loci were tested for cis-acting effects on all probes within 250 kb of each locus. Trans-effects of the SNPs on the 39,122 probes passing all QC on the microarray were also examined. From the analysis of cis-acting SNP effects, several SNPs in the MAPT region show significant association to multiple nearby probes, including two strongly correlated probes targeting the gene LOC644246 and the duplicated genes LRRC37A and LRRC37A2, and a third uncorrelated probe targeting the gene DCAKD. Significant cis-associations were also observed between SNPs and two probes targeting genes in the HLA region on chromosome 6. Expanding the association study to examine trans effects revealed an additional 23 SNP-probe associations reaching statistical significance (p

Suggested Citation

  • Jeanne C Latourelle & Alexandra Dumitriu & Tiffany C Hadzi & Thomas G Beach & Richard H Myers, 2012. "Evaluation of Parkinson Disease Risk Variants as Expression-QTLs," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-7, October.
    • Handle: RePEc:plo:pone00:0046199
    DOI: 10.1371/journal.pone.0046199
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0046199
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0046199&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0046199?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alexandra Dumitriu & Jeanne C Latourelle & Tiffany C Hadzi & Nathan Pankratz & Dan Garza & John P Miller & Jeffery M Vance & Tatiana Foroud & Thomas G Beach & Richard H Myers, 2012. "Gene Expression Profiles in Parkinson Disease Prefrontal Cortex Implicate FOXO1 and Genes under Its Transcriptional Regulation," PLOS Genetics, Public Library of Science, vol. 8(6), pages 1-11, June.
    2. Stephen B. Montgomery & Micha Sammeth & Maria Gutierrez-Arcelus & Radoslaw P. Lach & Catherine Ingle & James Nisbett & Roderic Guigo & Emmanouil T. Dermitzakis, 2010. "Transcriptome genetics using second generation sequencing in a Caucasian population," Nature, Nature, vol. 464(7289), pages 773-777, April.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Michael I Falola & Howard W Wiener & Nathan E Wineinger & Gary R Cutter & Robert P Kimberly & Jeffrey C Edberg & Donna K Arnett & Richard A Kaslow & Jianming Tang & Sadeep Shrestha, 2013. "Genomic Copy Number Variants: Evidence for Association with Antibody Response to Anthrax Vaccine Adsorbed," PLOS ONE, Public Library of Science, vol. 8(5), pages 1-9, May.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Federico Innocenti & Gregory M Cooper & Ian B Stanaway & Eric R Gamazon & Joshua D Smith & Snezana Mirkov & Jacqueline Ramirez & Wanqing Liu & Yvonne S Lin & Cliona Moloney & Shelly Force Aldred & Nat, 2011. "Identification, Replication, and Functional Fine-Mapping of Expression Quantitative Trait Loci in Primary Human Liver Tissue," PLOS Genetics, Public Library of Science, vol. 7(5), pages 1-16, May.
    2. Nuno A Fonseca & John Marioni & Alvis Brazma, 2014. "RNA-Seq Gene Profiling - A Systematic Empirical Comparison," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-10, September.
    3. Kyung-Won Hong & Seok Won Jeong & Myungguen Chung & Seong Beom Cho, 2014. "Association between Expression Quantitative Trait Loci and Metabolic Traits in Two Korean Populations," PLOS ONE, Public Library of Science, vol. 9(12), pages 1-13, December.
    4. Barbara E Stranger & Stephen B Montgomery & Antigone S Dimas & Leopold Parts & Oliver Stegle & Catherine E Ingle & Magda Sekowska & George Davey Smith & David Evans & Maria Gutierrez-Arcelus & Alkes P, 2012. "Patterns of Cis Regulatory Variation in Diverse Human Populations," PLOS Genetics, Public Library of Science, vol. 8(4), pages 1-13, April.
    5. Jungsoo Gim & Sungho Won & Taesung Park, 2016. "LPEseq: Local-Pooled-Error Test for RNA Sequencing Experiments with a Small Number of Replicates," PLOS ONE, Public Library of Science, vol. 11(8), pages 1-15, August.
    6. Faisal Shahla & Tutz Gerhard, 2017. "Missing value imputation for gene expression data by tailored nearest neighbors," Statistical Applications in Genetics and Molecular Biology, De Gruyter, vol. 16(2), pages 95-106, April.
    7. Eric O Johnson & Dana B Hancock & Nathan C Gaddis & Joshua L Levy & Grier Page & Scott P Novak & Cristie Glasheen & Nancy L Saccone & John P Rice & Michael P Moreau & Kimberly F Doheny & Jane M Romm &, 2015. "Novel Genetic Locus Implicated for HIV-1 Acquisition with Putative Regulatory Links to HIV Replication and Infectivity: A Genome-Wide Association Study," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-15, March.
    8. Thanh Nguyen & Asim Bhatti & Samuel Yang & Saeid Nahavandi, 2016. "RNA-Seq Count Data Modelling by Grey Relational Analysis and Nonparametric Gaussian Process," PLOS ONE, Public Library of Science, vol. 11(10), pages 1-18, October.
    9. Farnoosh Abbas-Aghababazadeh & Qian Li & Brooke L Fridley, 2018. "Comparison of normalization approaches for gene expression studies completed with high-throughput sequencing," PLOS ONE, Public Library of Science, vol. 13(10), pages 1-21, October.
    10. Kensuke Yamaguchi & Kazuyoshi Ishigaki & Akari Suzuki & Yumi Tsuchida & Haruka Tsuchiya & Shuji Sumitomo & Yasuo Nagafuchi & Fuyuki Miya & Tatsuhiko Tsunoda & Hirofumi Shoda & Keishi Fujio & Kazuhiko , 2022. "Splicing QTL analysis focusing on coding sequences reveals mechanisms for disease susceptibility loci," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    11. Alexandra C Nica & Leopold Parts & Daniel Glass & James Nisbet & Amy Barrett & Magdalena Sekowska & Mary Travers & Simon Potter & Elin Grundberg & Kerrin Small & Åsa K Hedman & Veronique Bataille & Jo, 2011. "The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study," PLOS Genetics, Public Library of Science, vol. 7(2), pages 1-9, February.
    12. Jean Francois Lefebvre & Emilio Vello & Bing Ge & Stephen B Montgomery & Emmanouil T Dermitzakis & Tomi Pastinen & Damian Labuda, 2012. "Genotype-Based Test in Mapping Cis-Regulatory Variants from Allele-Specific Expression Data," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-15, June.
    13. Laura L Elo & Benno Schwikowski, 2013. "Analysis of Time-Resolved Gene Expression Measurements across Individuals," PLOS ONE, Public Library of Science, vol. 8(12), pages 1-8, December.
    14. Sara Mostafavi & Alexis Battle & Xiaowei Zhu & Alexander E Urban & Douglas Levinson & Stephen B Montgomery & Daphne Koller, 2013. "Normalizing RNA-Sequencing Data by Modeling Hidden Covariates with Prior Knowledge," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-10, July.
    15. John Platig & Peter J Castaldi & Dawn DeMeo & John Quackenbush, 2016. "Bipartite Community Structure of eQTLs," PLOS Computational Biology, Public Library of Science, vol. 12(9), pages 1-17, September.
    16. Daria V Zhernakova & Eleonora de Klerk & Harm-Jan Westra & Anastasios Mastrokolias & Shoaib Amini & Yavuz Ariyurek & Rick Jansen & Brenda W Penninx & Jouke J Hottenga & Gonneke Willemsen & Eco J de Ge, 2013. "DeepSAGE Reveals Genetic Variants Associated with Alternative Polyadenylation and Expression of Coding and Non-coding Transcripts," PLOS Genetics, Public Library of Science, vol. 9(6), pages 1-15, June.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0046199. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.