A genomewide screen for chronic rhinosinusitis genes identifies a locus on chromosome 7q.
OBJECTIVE
Chronic rhinosinusitis (CRS) is an important public health problem with substantial impact on patient quality of life and health care costs. We hypothesized that genetic variation may be one factor that affects this disease.


METHODS
Identification of genetic variation underlying susceptibility to CRS using linkage analysis in a founder population.


METHODS
We studied a religious isolate that practices a communal lifestyle and shares common environmental exposures. Using physical examination, medical interviews, and a review of medical records, we identified eight individuals with CRS of 291 screened. These eight individuals were related to each other in a single 60 member, nine generation pedigree. A genome-wide screen for loci influencing susceptibility to CRS using 1123 genome-wide markers was conducted.


RESULTS
The largest linkage peak (P = .0023; 127.15 cM, equivalent to limit of detection = 2.01) was on chromosome 7q31.1-7q32.1, 7q31 (127.15 cM; 1-limit of detection support region: 115-135 cM) and included the CFTR locus. Genotyping of 38 mutations in the CFTR gene did not reveal variation accounting for this linkage signal.


CONCLUSIONS
Understanding the genes involved in CRS may lead to improvements in its diagnosis and treatment. Our results represent the first genome-wide screen for CRS and suggest that a locus on 7q31.1-7q32.1 influences disease susceptibility. This may be the CFTR gene or another nearby locus.
Pinto
Jayant M
JM
Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The University of Chicago, Chicago, Illinois 60637, USA. jpinto@surgery.bsd.uchicago.edu
Hayes
M Geoffrey
MG
Schneider
Daniel
D
Naclerio
Robert M
RM
Ober
Carole
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D002908:Chronic Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004247:DNA / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods*; D015894:Genome, Human; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D011110:Polymorphism, Genetic; D011159:Population Surveillance / Q000379:methods; D011379:Prognosis; D012220:Rhinitis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D012852:Sinusitis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D014481:United States / Q000453:epidemiology
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA