title: Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes.
abstract: BACKGROUND
  Asthma is a clinically heterogeneous disease caused by a complex interaction between genetic susceptibility and diverse environmental factors. In common with other complex diseases the lack of a standardized scheme to evaluate the phenotypic variability poses challenges in identifying the contribution of genes and environments to disease expression.
  
  
  OBJECTIVE
  To determine the minimum number of sets of features required to characterize subjects with asthma which will be useful in identifying important genetic and environmental contributors. Methods Probands aged 7-35 years with physician diagnosed asthma and symptomatic siblings were identified in 1022 nuclear families from 11 centres in six countries forming the Genetics of Asthma International Network. Factor analysis was used to identify distinct phenotypes from questionnaire, clinical, and laboratory data, including baseline pulmonary function, allergen skin prick test (SPT).
  
  
  RESULTS
  Five distinct factors were identified:(1) baseline pulmonary function measures [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], (2) specific allergen sensitization by SPT, (3) self-reported allergies, (4) symptoms characteristic of rhinitis and (5) symptoms characteristic of asthma. Replication in symptomatic siblings was consistent with shared genetic and/or environmental effects, and was robust across age groups, gender, and centres. Cronbach's alpha ranged from 0.719 to 0.983 suggesting acceptable internal scale consistencies. Derived scales were correlated with serum IgE, methacholine PC(20), age and asthma severity (interrupted sleep). IgE correlated with all three atopy-related factors, the strongest with the SPT factor whereas severity only correlated with baseline lung function, and with symptoms characteristic of rhinitis and of asthma.
  
  
  CONCLUSIONS
  In children and adolescents with established asthma, five distinct sets of correlated patient characteristics appear to represent important aspects of the disease. Factor scores as quantitative traits may be better phenotypes in epidemiological and genetic analyses than those categories derived from the presence or absence of combinations of +ve SPTs and/or elevated IgE.
authors.affiliation: Medical Genetics, GlaxoSmithKline, Research Triangle Park, NC, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Pillai
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.forename: E
authors.initials: E
authors.lastname: van den Oord
authors.forename: M
authors.initials: M
authors.lastname: Klotsman
authors.forename: K
authors.initials: K
authors.lastname: Barnes
authors.forename: K
authors.initials: K
authors.lastname: Carlsen
authors.forename: J
authors.initials: J
authors.lastname: Gerritsen
authors.forename: W
authors.initials: W
authors.lastname: Lenney
authors.forename: M
authors.initials: M
authors.lastname: Silverman
authors.forename: P
authors.initials: P
authors.lastname: Sly
authors.forename: J
authors.initials: J
authors.lastname: Sundy
authors.forename: J
authors.initials: J
authors.lastname: Tsanakas
authors.forename: A
authors.initials: A
authors.lastname: von Berg
authors.forename: M
authors.initials: M
authors.lastname: Whyte
authors.forename: H G
authors.initials: HG
authors.lastname: Ortega
authors.forename: W H
authors.initials: WH
authors.lastname: Anderson
authors.forename: P J
authors.initials: PJ
authors.lastname: Helms
mesh_terms: D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology; D001249:Asthma / Q000150:complications* / Q000175:diagnosis / Q000276:immunology / Q000503:physiopathology*; D016085:Bronchoconstrictor Agents; D002648:Child; D005163:Factor Analysis, Statistical; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D006967:Hypersensitivity / Q000150:complications*; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D016210:Methacholine Chloride; D010641:Phenotype; D012129:Respiratory Function Tests; D012220:Rhinitis / Q000503:physiopathology; D012720:Severity of Illness Index; D012882:Skin Tests; D014797:Vital Capacity
chemical_list: D000485:Allergens; D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride; D007073:Immunoglobulin E