Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

Journal article


Publication Details

Author(s): Krumbiegel M, Pasutto F, Schlötzer-Schrehardt U, Uebe S, Zenkel M, Mardin CY, Weisschuh N, Paoli D, Gramer E, Becker C, Ekici AB, Weber BHF, Nuernberg P, Kruse F, Reis A
Journal: European journal of human genetics
Publication year: 2011
Volume: 19
Journal issue: 2
Pages range: 186-93
ISSN: 1018-4813


Abstract


Genetic and nongenetic factors contribute to development of pseudoexfoliation (PEX) syndrome, a complex, age-related, generalized matrix process frequently associated with glaucoma. To identify specific genetic variants underlying its etiology, we performed a genome-wide association study (GWAS) using a DNA-pooling approach. Therefore, equimolar amounts of DNA samples of 80 subjects with PEX syndrome, 80 with PEX glaucoma (PEXG) and 80 controls were combined into separate pools and hybridized to 500K SNP arrays (Affymetrix). Array probe intensity data were analyzed and visualized with expressly developed software tools GPFrontend and GPGraphics in combination with GenePool software. For replication, independent German cohorts of 610 unrelated patients with PEX/PEXG and 364 controls as well as Italian cohorts of 249 patients and 190 controls were used. Of 19, 17 SNPs showing significant allele frequency difference in DNA pools were confirmed by individual genotyping. Further single genotyping at CNTNAP2 locus revealed association between PEX/PEXG for two SNPs, which was confirmed in an independent German but not the Italian cohort. Both SNPs remained significant in the combined German cohorts even after Bonferroni correction (rs2107856: P(c)=0.0108, rs2141388: P(c)=0.0072). CNTNAP2 was found to be ubiquitously expressed in all human ocular tissues, particularly in retina, and localized to cell membranes of epithelial, endothelial, smooth muscle, glial and neuronal cells. Confirming efficiency of GWAS with DNA-pooling approach by detection of the known LOXL1 locus, our study data show evidence for association of CNTNAP2 with PEX syndrome and PEXG in German patients.



FAU Authors / FAU Editors

Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Kruse, Friedrich Prof. Dr.
Lehrstuhl für Augenheilkunde
Schlötzer-Schrehardt, Ursula apl. Prof. Dr.
Medizinische Fakultät
Uebe, Steffen Dr. rer. nat.
Humangenetisches Institut
Zenkel, Matthias Dr. rer. nat.
Augenklinik


External institutions with authors

Monfalcone Hospital
Universität Köln
Universität Regensburg
Universitätsklinikum Tübingen
Universitätsklinikum Würzburg


How to cite

APA:
Krumbiegel, M., Pasutto, F., Schlötzer-Schrehardt, U., Uebe, S., Zenkel, M., Mardin, C.Y.,... Reis, A. (2011). Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome. European journal of human genetics, 19(2), 186-93. https://dx.doi.org/10.1038/ejhg.2010.144

MLA:
Krumbiegel, Mandy, et al. "Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome." European journal of human genetics 19.2 (2011): 186-93.

BibTeX: 

Last updated on 2019-10-06 at 07:13