Initial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: Chromosomes 2, 11, 13, 14, and X
✍ Scribed by Stine, O. Colin; McMahon, Francis J.; Chen, Li-shiun; Xu, Jianfeng; Meyers, Deborah A.; MacKinnon, Dean F.; Simpson, Sylvia; McInnis, Melvin G.; Rice, John P.; Goate, Alison; Reich, Theodore; Edenberg, Howard J.; Foroud, Tatiana; Nurnberger, John I.; Detera-Wadleigh, Sevilla D.; Goldin, Lynn R.; Guroff, Juliet; Gershon, Elliot S.; Blehar, Mary C.; DePaulo, J. Raymond
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 228 KB
- Volume
- 74
- Category
- Article
- ISSN
- 0148-7299
No coin nor oath required. For personal study only.
✦ Synopsis
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 disorderrecurrent 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 i = 1.5 could be excluded in <10% of the genetic distance studied, while a locus conferring i = 3 or greater could be excluded across at least 96%. The autosomal region that could not be excluded even with i = 5 was near 13q14-32. In this region, two-point affected sib-pair analyses revealed a pair of consecutive loci with ex-cess 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 i = 3.6 in affected brotherbrother pairs, while a locus linked to the markers in Xq26-28 would have i у 1.9 in affected sister-sister pairs. The results on 13q14-32, Xp22, and Xq26-28 suggest areas of interest for further studies. Am.