title: A genome-wide linkage scan for distinct subsets of schizophrenia characterized by age at onset and neurocognitive deficits.
abstract: BACKGROUND
  As schizophrenia is genetically and phenotypically heterogeneous, targeting genetically informative phenotypes may help identify greater linkage signals. The aim of the study is to evaluate the genetic linkage evidence for schizophrenia in subsets of families with earlier age at onset or greater neurocognitive deficits.
  
  
  METHODS
  Patients with schizophrenia (n  =  1,207) and their first-degree relatives (n  =  1,035) from 557 families with schizophrenia were recruited from six data collection field research centers throughout Taiwan. Subjects completed a face-to-face semi-structured interview, the Continuous Performance Test (CPT), the Wisconsin Card Sorting Test, and were genotyped with 386 microsatellite markers across the genome.
  
  
  RESULTS
  A maximum nonparametric logarithm of odds (LOD) score of 4.17 at 2q22.1 was found in 295 families ranked by increasing age at onset, which had significant increases in the maximum LOD score compared with those obtained in initial linkage analyses using all available families. Based on this subset, a further subsetting by false alarm rate on the undegraded and degraded CPT obtained further increase in the nested subset-based LOD on 2q22.1, with a score of 7.36 in 228 families and 7.71 in 243 families, respectively.
  
  
  CONCLUSIONS
  We found possible evidence of linkage on chromosome 2q22.1 in families of schizophrenia patients with more CPT false alarm rates nested within the families with younger age at onset. These results highlight the importance of incorporating genetically informative phenotypes in unraveling the complex genetics of schizophrenia.
authors: College of Public Health, Research Center for Genes and Institute of Epidemiology and Preventive Medicine, Environment and Human Health, National Taiwan University, Taipei, Taiwan.
authors: Yin-Ju
authors: YJ
authors: Lien
authors: Po-Chang
authors: PC
authors: Hsiao
authors: Chih-Min
authors: CM
authors: Liu
authors: Stephen V
authors: SV
authors: Faraone
authors: Ming T
authors: MT
authors: Tsuang
authors: Hai-Gwo
authors: HG
authors: Hwu
authors: Wei J
authors: WJ
authors: Chen
mesh_terms: D017668:Age of Onset; D003072:Cognition Disorders / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D012559:Schizophrenia / Q000145:classification / Q000453:epidemiology* / Q000235:genetics / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D055815:Young Adult