Genome-wide scan and conditional analysis in bipolar disorder: evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees

Melvin G McInnis; Danielle M Dick; Virginia L Willour; Dimitrios Avramopoulos; Dean F MacKinnon; Sylvia G Simpson; James B Potash; Howard J Edenberg; Elizabeth S Bowman; Francis J McMahon; Carrie Smiley; Jennifer L Chellis; Yuqing Huo; Tyra Diggs; Eric T Meyer; Marvin Miller; Amy T Matteini; N.Leela Rau; J.Raymond DePaulo; Elliot S Gershon; Judith A Badner; John P Rice; Alison M Goate; Sevilla D Detera-Wadleigh; John I Nurnberger; Theodore Reich; Peter P Zandi; Tatiana M Foroud

doi:10.1016/j.biopsych.2003.08.001

Back

Genome-wide scan and conditional analysis in bipolar disorder: evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees

Journal article

Peer reviewed

Genome-wide scan and conditional analysis in bipolar disorder: evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees

Melvin G McInnis, Danielle M Dick, Virginia L Willour, Dimitrios Avramopoulos, Dean F MacKinnon, Sylvia G Simpson, James B Potash, Howard J Edenberg, Elizabeth S Bowman, Francis J McMahon, …

Biological psychiatry (1969), Vol.54(11), pp.1265-1273

2003

DOI: 10.1016/j.biopsych.2003.08.001

PMID: 14643094

View Online

Abstract

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. 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. 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. 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.

Genetics

conditional analysis

Bipolar disorder

linkage

Details

Title: Subtitle: Genome-wide scan and conditional analysis in bipolar disorder: evidence for genomic interaction in the National Institute of Mental Health genetics initiative bipolar pedigrees
Creators: Melvin G McInnis - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Danielle M Dick - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
Virginia L Willour - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Dimitrios Avramopoulos - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Dean F MacKinnon - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Sylvia G Simpson - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
James B Potash - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Howard J Edenberg - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
Elizabeth S Bowman - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
Francis J McMahon - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Carrie Smiley - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
Jennifer L Chellis - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Yuqing Huo - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Tyra Diggs - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Eric T Meyer - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
Marvin Miller - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
Amy T Matteini - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
N.Leela Rau - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
J.Raymond DePaulo - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Elliot S Gershon - Department of Psychiatry (FJM, ESG, JAB), University of Chicago, Chicago, Illinois, USA
Judith A Badner - Department of Psychiatry (FJM, ESG, JAB), University of Chicago, Chicago, Illinois, USA
John P Rice - Department of Psychiatry (JPR, AMG, TR), Washington University School of Medicine, St. Louis, Missouri, USA
Alison M Goate - Department of Psychiatry (JPR, AMG, TR), Washington University School of Medicine, St. Louis, Missouri, USA
Sevilla D Detera-Wadleigh - Mood and Anxiety Disorders Unit, Intramural Program (FJM, ESG, JAB, SDD-W) National Institute of Mental Health, Bethesda, Maryland, USA
John I Nurnberger - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
Theodore Reich - Department of Psychiatry (JPR, AMG, TR), Washington University School of Medicine, St. Louis, Missouri, USA
Peter P Zandi - Department of Psychiatry and Behavioral Sciences (MGM, VLW, DA, DFM, SGS, JBP, FJM, JLC, YH, TD, ATM, JRD, PPZ), Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Tatiana M Foroud - Institute of Psychiatric Research (DMD, HJE, ESB, CS, ETM, MM, NLR, JIN, TMF), Indiana University School of Medicine, Indianapolis, Indiana, USA
Resource Type: Journal article
Publication Details: Biological psychiatry (1969), Vol.54(11), pp.1265-1273
DOI: 10.1016/j.biopsych.2003.08.001
PMID: 14643094
NLM abbreviation: Biol Psychiatry
ISSN: 0006-3223
eISSN: 1873-2402
Publisher: Elsevier Inc
Language: English
Date published: 2003
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003952102771

Metrics

29 Record Views

72 Times Cited - Web of Science