title: Loci on chromosomes 6q and 6p interact to increase susceptibility to bipolar affective disorder in the national institute of mental health genetics initiative pedigrees.
abstract: BACKGROUND
  We have reported genetic linkage between bipolar disorder and markers on chromosome 6q16.3-22.1 in the National Institute of Mental Health Genetics Initiative wave 3 pedigrees. Here we test for: 1) robustness of the linkage to differing analysis methods, genotyping error, and gender-specific maps; 2) parent-of-origin effects; and 3) interaction with markers within the schizophrenia linkage region on chromosome 6p.
  
  
  METHODS
  Members of 245 families ascertained through a sibling pair affected with bipolar I or schizoaffective-bipolar disorder were genotyped with 18 markers spanning chromosome 6. Nonparametric linkage analysis was performed.
  
  
  RESULTS
  Linkage to 6q is robust to analysis method, gender-specific map differences, and genotyping error. The locus confers a 1.4-fold increased risk. Affected siblings share the maternal more often than the paternal chromosome (p =.006), which could reflect a maternal parent-of-origin effect. There is a positive correlation between family-specific linkage scores on 6q and those on 6p22.2 (r =.26; p <.0001). Linkage analysis for each locus conditioned on evidence of linkage to the other increases the evidence for linkage at both loci (p <.0005). Logarithm of the odds (LOD) scores increased from 2.26 to 5.42 on 6q and from.35 to 2.26 on 6p22.2.
  
  
  CONCLUSIONS
  These results support linkage of bipolar disorder to 6q, uncover a maternal parent-of-origin effect, and demonstrate an interaction of this locus with one on chromosome 6p22.2, previously linked only to schizophrenia.
authors.affiliation: Genetic Basis of Mood and Anxiety Disorders, Mood and Anxiety Program, Bethesda, USA. schulze@zi-mannheim.de
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Schulze
authors.forename: Silvia
authors.initials: S
authors.lastname: Buervenich
authors.forename: Judith A
authors.initials: JA
authors.lastname: Badner
authors.forename: C J M
authors.initials: CJ
authors.lastname: Steele
authors.forename: Sevilla D
authors.initials: SD
authors.lastname: Detera-Wadleigh
authors.forename: Danielle
authors.initials: D
authors.lastname: Dick
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Dean F
authors.initials: DF
authors.lastname: MacKinnon
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
authors.forename: Wade H
authors.initials: WH
authors.lastname: Berrettini
authors.forename: William
authors.initials: W
authors.lastname: Byerley
authors.forename: William
authors.initials: W
authors.lastname: Coryell
authors.forename: J Raymond
authors.initials: JR
authors.lastname: DePaulo
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.forename: John R
authors.initials: JR
authors.lastname: Kelsoe
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Murphy
authors.forename: Theodore
authors.initials: T
authors.lastname: Reich
authors.forename: William
authors.initials: W
authors.lastname: Scheftner
authors.forename: John I
authors.initials: JI
authors.lastname: Nurnberger
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
mesh_terms: D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D004843:Epistasis, Genetic; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008126:Lod Score; D008297:Male; D009315:National Institute of Mental Health (U.S.); D010375:Pedigree; D011618:Psychotic Disorders / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D014481:United States / Q000453:epidemiology