TY - JOUR
T1 - Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees
T2 - Chromosomes 2, 11, 13, 14, and x
AU - Stine, O. Colin
AU - McMahon, Francis J.
AU - Chen, Li Shiun
AU - Xu, Jianfeng
AU - Meyers, Deborah A.
AU - MacKinnon, Dean F.
AU - Simpson, Sylvia
AU - McInnis, Melvin G.
AU - Rice, John P.
AU - Goate, Alison
AU - Reich, Theodore
AU - Edenberg, Howard J.
AU - Foroud, Tatiana
AU - Nurnberger, John I.
AU - Detera-Wadleigh, Sevilla D.
AU - Goldin, Lynn R.
AU - Guroff, Juliet
AU - Gershon, Elliot S.
AU - Blehar, Mary C.
AU - DePaulo, J. Raymond
PY - 1997
Y1 - 1997
N2 - We report on an initial genome screen of 540 individuals from 97 families collected as part of the NIMH Genetics Initiative Bipolar Group. Among the individuals studied, 232 were diagnosed with bipolar (BP) I, 72 with BPII, 88 with major depressive disorder recurrent type (UPR), and 32 with schizoaffective disorder, bipolar type (SA/BP). A total of 53 markers on chromosomes 2, 11, 13, 14, and X (average spacing: 11.5 cM) were studied at Johns Hopkins University. Tests for linkage were performed using nonparametric affected sib-pair and whole pedigree methods with three definitions of affected status. Three regions of interest were identified (13q14-32, Xp22, and Xq26-28). On chromosomes 2, 11, and 14, a disease locus with relative risk λ(i) = 1.5 could be excluded in <10% of the genetic distance studied, while a locus conferring λ(i) = 3 or greater could be excluded across at least 96%. The autosomal region that could not be excluded even with λ(i) = 5 was near 13q14-32. In this region, two-point affected sib-pair analyses revealed a pair of consecutive loci with excess sharing (P < 0.05) and a multipoint affected sib-pair LOD score of 1.12. On the X chromosome, nonparametric multipoint affected sib-pair analyses revealed peak total LOD scores of 0.94 on Xp22 and 1.34 on Xq26-28. A locus linked to the markers in Xp22 would have λ(i) = 3.6 in affected brother-brother pairs, while a locus linked to the markers in Xq26-28 would have λ(i) ≤ 1.9 in affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest areas of interest for further studies.
AB - We report on an initial genome screen of 540 individuals from 97 families collected as part of the NIMH Genetics Initiative Bipolar Group. Among the individuals studied, 232 were diagnosed with bipolar (BP) I, 72 with BPII, 88 with major depressive disorder recurrent type (UPR), and 32 with schizoaffective disorder, bipolar type (SA/BP). A total of 53 markers on chromosomes 2, 11, 13, 14, and X (average spacing: 11.5 cM) were studied at Johns Hopkins University. Tests for linkage were performed using nonparametric affected sib-pair and whole pedigree methods with three definitions of affected status. Three regions of interest were identified (13q14-32, Xp22, and Xq26-28). On chromosomes 2, 11, and 14, a disease locus with relative risk λ(i) = 1.5 could be excluded in <10% of the genetic distance studied, while a locus conferring λ(i) = 3 or greater could be excluded across at least 96%. The autosomal region that could not be excluded even with λ(i) = 5 was near 13q14-32. In this region, two-point affected sib-pair analyses revealed a pair of consecutive loci with excess sharing (P < 0.05) and a multipoint affected sib-pair LOD score of 1.12. On the X chromosome, nonparametric multipoint affected sib-pair analyses revealed peak total LOD scores of 0.94 on Xp22 and 1.34 on Xq26-28. A locus linked to the markers in Xp22 would have λ(i) = 3.6 in affected brother-brother pairs, while a locus linked to the markers in Xq26-28 would have λ(i) ≤ 1.9 in affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest areas of interest for further studies.
KW - Affective disorder
KW - Linkage
KW - Occlusion mapping
UR - http://www.scopus.com/inward/record.url?scp=17544402946&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1096-8628(19970531)74:3<263::AID-AJMG5>3.0.CO;2-R
DO - 10.1002/(SICI)1096-8628(19970531)74:3<263::AID-AJMG5>3.0.CO;2-R
M3 - Article
C2 - 9184308
AN - SCOPUS:17544402946
SN - 1552-4841
VL - 74
SP - 263
EP - 269
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 3
ER -