A genome-wide association study for age-related hearing impairment in the Saami.
This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the burden of multiple testing, we applied principal component (PC) analysis to the multivariate audiometric phenotype. The first three PCs captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100 K chip. To account for multiple levels of relatedness among subjects, as well as for population stratification, association testing was performed using a mixed model. We summarised the top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55 x 10(-7)), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, the SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream from the metabotropic glutamate receptor-7 gene (GRM7). As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene.
Van Laer
Lut
L
Department of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Huyghe
Jeroen R
JR
Hannula
Samuli
S
Van Eyken
Els
E
Stephan
Dietrich A
DA
Mäki-Torkko
Elina
E
Aikio
Pekka
P
Fransen
Erik
E
Lysholm-Bernacchi
Alana
A
Sorri
Martti
M
Huentelman
Matthew J
MJ
Van Camp
Guy
G
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000502:physiology; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D034381:Hearing Loss / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology; D012537:Scandinavian and Nordic Countries / Q000208:ethnology; D054928:Validation Studies as Topic; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology
C101002:IQGAP2 protein, human; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D020703:ras GTPase-Activating Proteins