Genomewide scan of affected relative pairs using the NIMH Genetics Initiative Bipolar affective Disorder pedigrees

T. Foroud, P. F. Castellucio, D. L. Koller, H. J. Edenberg, A. Goate, S. Detera-Wadleigh, O. C. Stine, F. J. McMahon, M. G. McInnis, J. Rice, M. Blehar, L. R. Goldin, J. Badner, J. Guroff, T. Reich, J. R. DePaulo, E. Gershon, J. I. Nurnberger

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Abstract

As part of a four-center NIMH Genetics Initiative on Bipolar Disorder, a genome screen using 366 markers was performed on 540 DNAs from 97 families, enriched for affected relative pairs. This is the largest commonly ascertained and assessed linkage sample and includes 232 subjects diagnosed with bipolar I (BPI), 32 schizoaffective, bipolar type (SABP), 72 bipolar II (BPII), and 88 unipolar recurrent depression (UPR). Affected individuals under model I included those with a diagnosis of BPI or SABP; model II affection included model I plus BPII; and model III included model II plus UPR. There were 227, 324, and 412 affected relative pairs under models I, II, and III, respectively. Previous analyses of this data set had utilized primarily affected sibling pair methods of nonparametric linkage analyses. We report the results of nonparametric linkage analyses with the extended pedigree structure using the program Genehunter Plus. The most significant result was a lod score of 2.5 obtained on chromosome 10 near the marker D10S1423 with model II. In this region, the model I lod score was 1.50 and the model III lod score was 1.30. Other regions with lod scores over 1.50 for any of the three models included chromosomes 6 (model I), 8 (model III), 9 (model I), 14 (model I), 16 (model III), 17 (models I and II), 20 (model I). Additional markers are being analyzed in these regions and a replication sample is currently being genotyped to confirm these findings.

Original languageEnglish
Pages (from-to)462
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume81
Issue number6
StatePublished - Nov 6 1998

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