A genome-wide search for schizophrenia susceptibility genes

Am J Med Genet. 1998 Sep 7;81(5):364-76. doi: 10.1002/(sici)1096-8628(19980907)81:5<364::aid-ajmg4>3.0.co;2-t.

Abstract

We completed a systematic genome-wide search for evidence of loci linked to schizophrenia using a collection of 70 pedigrees containing multiple affected individuals according to three phenotype classifications: schizophrenia only (48 pedigrees; 70 sib-pairs); schizophrenia plus schizoaffective disorder (70 pedigrees; 101 sib-pairs); and a broad category consisting of schizophrenia, schizoaffective disorder, paranoid or schizotypal personality disorder, psychosis not otherwise specified (NOS), delusional disorder, and brief reactive psychosis (70 pedigrees; 111 sib-pairs). All 70 families contained at least one individual affected with chronic schizophrenia according to DSM-III-R criteria. Three hundred and thirty-eight markers spanning the genome were typed in all pedigrees for an average resolution of 10.5 cM (range, 0-31 cM) and an average heterozygosity of 74.3% per marker. The data were analyzed using multipoint nonparametric allele-sharing and traditional two-point lod score analyses using dominant and recessive, affecteds-only models. Twelve chromosomes (1, 2, 4, 5, 8, 10, 11, 12, 13, 14, 16, and 22) had at least one region with a nominal P value <0.05, and two of these chromosomes had a nominal P value <0.01 (chromosomes 13 and 16), using allele-sharing tests in GENEHUNTER. Five chromosomes (1, 2, 4, 11, and 13) had at least one marker with a lod score >2.0, allowing for heterogeneity. These regions will be saturated with additional markers and investigated in a new, larger set of families to test for replication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosome Mapping
  • Female
  • Genetic Linkage*
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Humans
  • Male
  • Schizophrenia / genetics*

Substances

  • Genetic Markers