title: A genome-wide screen for acrophobia susceptibility loci in a Finnish isolate.
abstract: Acrophobia, an abnormal fear of heights, is a specific phobia characterized as apprehension cued by the occurrence or anticipation of elevated spaces. It is considered a complex trait with onset influenced by both genetic and environmental factors. Identification of genetic risk variants would provide novel insight into the genetic basis of the fear of heights phenotype and contribute to the molecular-level understanding of its aetiology. Genetic isolates may facilitate identification of susceptibility alleles due to reduced genetic heterogeneity. We took advantage of an internal genetic isolate in Finland in which a distinct acrophobia phenotype appears to be segregating in pedigrees originally ascertained for schizophrenia. We conducted parametric, nonparametric, joint linkage and linkage disequilibrium analyses using a microsatellite marker panel, genotyped in families to search for chromosomal regions correlated with acrophobia. Our results implicated a few regions with suggestive evidence for linkage on chromosomes 4q28 (LOD = 2.17), 8q24 (LOD = 2.09) and 13q21-q22 (LOD = 2.22). We observed no risk haplotypes shared between different families. These results suggest that genetic predisposition to acrophobia in this genetic isolate is unlikely to be mediated by a small number of shared high-risk alleles, but rather has a complex genetic architecture.
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Zuzanna
authors.initials: Z
authors.lastname: Misiewicz
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.|Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: Tero
authors.initials: T
authors.lastname: Hiekkalinna
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.|Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Development of Work and Work Organizations, Finnish Institute of Occupational Health, Helsinki, Finland.
authors.forename: Tiina
authors.initials: T
authors.lastname: Paunio
authors.affiliation: Department of Medical Genetics, University of Helsinki, Helsinki, Finland.
authors.forename: Teppo
authors.initials: T
authors.lastname: Varilo
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.|Department of Psychiatry, Department of Genetics and Development, and Gertrude H. Sergievsky Center, Columbia University, New York NY, USA.|Division of Medical Genetics, New York State Psychiatric Institute, New York NY, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Terwilliger
authors.affiliation: Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Partonen
authors.affiliation: Department of Biosciences, University of Helsinki, Helsinki, Finland.|Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
authors.forename: Iiris
authors.initials: I
authors.lastname: Hovatta
mesh_terms: D000483:Alleles; D059031:Anticipation, Psychological / Q000502:physiology*; D002874:Chromosome Mapping; D005260:Female; D005387:Finland; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D010698:Phobic Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics