Genetic variants in the RELN gene are associated with otosclerosis in multiple European populations.
Otosclerosis is a common form of hearing loss characterized by abnormal bone remodeling in the otic capsule. It is considered a complex disease caused by both genetic and environmental factors. In a previous study, we identified a region on chr7q22.1 located in the RELN gene that is associated with otosclerosis in Belgian-Dutch and French populations. Evidence for allelic heterogeneity was found in this chromosomal region in the form of two independent signals. To confirm this finding, we have completed a replication study that includes four additional populations from Europe (1,141 total samples). Several SNPs in this region replicated in these populations separately. While the power to detect significant association in each population is small, when all four populations are combined, six of seven SNPs replicate and show an effect in the same direction as in the previous populations. We also confirmed the presence of allelic heterogeneity in this region. These data further implicate RELN in the pathogenesis of otosclerosis. Functional research is warranted to determine the pathways through which RELN acts in the pathogenesis of otosclerosis.
Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium. isabelle.schrauwen@ua.ac.be
Isabelle
I
Schrauwen
Megan
M
Ealy
Erik
E
Fransen
Kathleen
K
Vanderstraeten
Melissa
M
Thys
Nicole C
NC
Meyer
Marcel
M
Cosgarea
Alex
A
Huber
Manuela
M
Mazzoli
Markus
M
Pfister
Richard J H
RJ
Smith
Guy
G
Van Camp
D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D018740:Genetic Heterogeneity; D005838:Genotype; D005858:Germany; D006320:Hearing Tests; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010040:Otosclerosis / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000091042:Reelin Protein; D012383:Romania; D012697:Serine Endopeptidases / Q000235:genetics*; D013557:Switzerland
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; D012697:Serine Endopeptidases