@article{610bc730f12b4f14ab73a98a04b019be,
title = "Genome-wide scan and conditional analysis in bipolar disorder: Evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees",
abstract = "Background: In 1989 the National Institute of Mental Health began a collaborative effort to identify genes for bipolar disorder. The first 97 pedigrees showed evidence of linkage to chromosomes 1, 6, 7, 10, 16, and 22 (Nurnberger et al 1997). An additional 56 bipolar families have been genotyped, and the combined sample of 153 pedigrees studied. Methods: Three hierarchical affection status models were analyzed with 513 simple sequence repeat markers; 298 were common across all pedigrees. The primary analysis was a nonparametric genome-wide scan. We performed conditional analyses based on epistasis or heterogeneity for five regions. Results: One region, on 16p13, was significant at the genome-wide p < .05 level. Four additional chromosomal regions (20p12, 11p15, 6q24, and 10p12) showed nominally significant linkage findings (p ≤ .01). Conditional analysis assuming epistasis identified a significant increase in linkage at four regions. Families linked to 6q24 showed a significant increase in nonparametric logarithms of the odds (NPL) scores at 5q11 and 7q21. Epistasis also was observed between 20p12 and 13q21, and 16p13 and 9q21. Conclusions: The findings are presented in rank order of nominal significance. Several of these regions have been previously implicated in independent studies of either bipolar disorder or schizophrenia. The strongest finding is at 16p13 at D16S748 with an NPL of 3.3, there is evidence of epistasis between this locus and 9q21. Application of conditional analyses is potentially useful in larger sample collections to identify susceptibility genes of modest influence that may not be identified in a genome-wide scan aimed to identify single gene effects.",
keywords = "Bipolar disorder, Conditional analysis, Genetics, Linkage",
author = "McInnis, {Melvin G.} and Dick, {Danielle M.} and Willour, {Virginia L.} and Dimitrios Avramopoulos and MacKinnon, {Dean F.} and Simpson, {Sylvia G.} and Potash, {James B.} and Edenberg, {Howard J.} and Bowman, {Elizabeth S.} and McMahon, {Francis J.} and Carrie Smiley and Chellis, {Jennifer L.} and Yuqing Huo and Tyra Diggs and Meyer, {Eric T.} and Marvin Miller and Matteini, {Amy T.} and Rau, {N. Leela} and DePaulo, {J. Raymond} and Gershon, {Elliot S.} and Badner, {Judith A.} and Rice, {John P.} and Goate, {Alison M.} and Detera-Wadleigh, {Sevilla D.} and Nurnberger, {John I.} and Theodore Reich and Zandi, {Peter P.} and Foroud, {Tatiana M.}",
note = "Funding Information: We thank all the families who have participated in these studies. We acknowledge the cadre of research assistants, who over the years have worked tirelessly to ensure the success of this collaborative effort. This work represents the collaborative efforts of the four sites of the National Institute of Mental Health (NIMH) Genetics Initiative for Bipolar Disorder supported by Grant Nos. U01 MH46282, 54794, 46280, 54723, 46274, and 54701. At Indiana University, this work was funded by Grant No. R01 MH59545 and a grant from the Indiana Division of Mental Health. At Johns Hopkins University, the work was supported by Grant No. R01-MH-59533 (JRD, MGM) and in part by Grant Nos. K20-MH-01088 (MGM) and National Alliance for Research on Schizophrenia and Depression (NARSAD) (JRD, MGM, DFM, SGS). Elliot Gershon, M.D., formerly of the NIMH Intramural Program and now of the University of Chicago, was supported by Grant Nos. R01 MH59535, R01 MH61613, and a NARSAD Distinguished Investigator Award and acknowledges the contribution of Mrs. Anita Kaskel Roe. Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",
year = "2003",
month = dec,
day = "1",
doi = "10.1016/j.biopsych.2003.08.001",
language = "English (US)",
volume = "54",
pages = "1265--1273",
journal = "Biological psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "11",
}