TY - JOUR
T1 - Genomewide linkage analyses of bipolar disorder
T2 - A new sample of 250 pedigrees from the national institute of mental health genetics initiative
AU - Dick, Danielle M.
AU - Foroud, Tatiana
AU - Flury, Leah
AU - Bowman, Elizabeth S.
AU - Miller, Marvin J.
AU - Rau, N. Leela
AU - Moe, P. Ryan
AU - Samavedy, Nalini
AU - El-Mallakh, Rif
AU - Manji, Husseini
AU - Glitz, Debra A.
AU - Meyer, Eric T.
AU - Smiley, Carrie
AU - Hahn, Rhoda
AU - Widmark, Clifford
AU - McKinney, Rebecca
AU - Sutton, Laura
AU - Ballas, Christos
AU - Grice, Dorothy
AU - Berrettini, Wade
AU - Byerley, William
AU - Coryell, William
AU - DePaulo, Raymond
AU - MacKinnon, Dean F.
AU - Gershon, Elliot S.
AU - Kelsoe, John R.
AU - McMahon, Francis J.
AU - McInnis, Melvin
AU - Murphy, Dennis L.
AU - Reich, Theodore
AU - Scheftner, William
AU - Nurnberger, John I.
N1 - Funding Information:
We gratefully acknowledge support from the NIMH (R01s MH59545 [to J.I.N.], MH60068 [to W.B.], MH59567 [to J.R.K.], R0159553 [to W.H.B.]). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to Johns Hopkins University, contract N01-HG-65403. Preparation of this manuscript was also supported by AA13358 (to D.D.) and AA00285 (to T.F.). We also acknowledge John Hennion, M.S., Jennifer Khalid, R.N., and other interviewers and best-estimate diagnosticians, for subject ascertainment and assessment, as well as Howard Edenberg, Ph.D., for helpful suggestions on a previous draft of this manuscript. We are grateful to the patients and family members who generously participated in this research and to the treatment facilities and other organizations that collaborated with us in identifying families.
PY - 2003/7/1
Y1 - 2003/7/1
N2 - We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P < .05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P < .10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.
AB - We conducted genomewide linkage analyses on 1,152 individuals from 250 families segregating for bipolar disorder and related affective illnesses. These pedigrees were ascertained at 10 sites in the United States, through a proband with bipolar I affective disorder and a sibling with bipolar I or schizoaffective disorder, bipolar type. Uniform methods of ascertainment and assessment were used at all sites. A 9-cM screen was performed by use of 391 markers, with an average heterozygosity of 0.76. Multipoint, nonparametric linkage analyses were conducted in affected relative pairs. Additionally, simulation analyses were performed to determine genomewide significance levels for this study. Three hierarchical models of affection were analyzed. Significant evidence for linkage (genomewide P < .05) was found on chromosome 17q, with a peak maximum LOD score of 3.63, at the marker D17S928, and on chromosome 6q, with a peak maximum LOD score of 3.61, near the marker D6S1021. These loci met both standard and simulation-based criteria for genomewide significance. Suggestive evidence of linkage was observed in three other regions (genomewide P < .10), on chromosomes 2p, 3q, and 8q. This study, which is based on the largest linkage sample for bipolar disorder analyzed to date, indicates that several genes contribute to bipolar disorder.
UR - https://www.scopus.com/pages/publications/0038389850
U2 - 10.1086/376562
DO - 10.1086/376562
M3 - Article
C2 - 12772088
AN - SCOPUS:0038389850
SN - 0002-9297
VL - 73
SP - 107
EP - 114
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -