Genetics of recurrent early-onset major depression (GenRED): Final genome scan report

Peter Holmans, Myrna M. Weissman, George S. Zubenko, William A. Scheftner, Raymond R. Crowe, J Raymond Depaulo, James A. Knowles, Wendy N. Zubenko, Kathleen Murphy-Eberenz, Diana H. Marta, Sandra Boutelle, Melvin G. McInnis, Philip Adams, Madeline Gladis, Jo Steele, Erin B. Miller, James Bennett Potash, Dean F Mackinnon, Douglas F. Levinson

Research output: Contribution to journalArticle

Abstract

Objective: The authors carried out a genomewide linkage scan to identify chromosomal regions likely to contain genes that contribute to susceptibility to recurrent early-onset major depressive disorder, the form of the disorder with the greatest reported risk to relatives of index cases. Method: Microsatellite DNA markers were studied in 656 families with two or more such cases (onset before age 31 in probands and age 41 in other relatives), including 1,494 informative "all possible" affected relative pairs (there were 894 independent affected sibling pairs). Analyses included a primary multipoint allele-sharing analysis (with ALLEGRO) and a secondary logistic regression analysis taking the sex of each relative pair into account (male-male, male-female, female-female). Results: Genomewide suggestive evidence for linkage was observed on chromosome 15q25-q26 (at 105.4 centimorgans [cM]). The authors previously reported genomewide significant linkage in this region in the first 297 families. In the secondary analysis, after empirical genomewide correction for multiple testing, suggestive linkage results were observed on chromosome 17p12 (28.0 cM, excess sharing in male-male and male-female pairs) and on chromosome 8p22-p21.3 (25.1 cM, excess sharing in male-male pairs). Conclusions: These regions of chromosomes 15q, 17p, and 8p might contain genes that contribute to susceptibility to major depression and related disorders. Evidence for linkage has been reported independently in the same regions of chromosome 15q for major depression and of chromosome 8p for related personality traits.

Original languageEnglish (US)
Pages (from-to)248-258
Number of pages11
JournalAmerican Journal of Psychiatry
Volume164
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

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ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Holmans, P., Weissman, M. M., Zubenko, G. S., Scheftner, W. A., Crowe, R. R., Depaulo, J. R., Knowles, J. A., Zubenko, W. N., Murphy-Eberenz, K., Marta, D. H., Boutelle, S., McInnis, M. G., Adams, P., Gladis, M., Steele, J., Miller, E. B., Potash, J. B., Mackinnon, D. F., & Levinson, D. F. (2007). Genetics of recurrent early-onset major depression (GenRED): Final genome scan report. American Journal of Psychiatry, 164(2), 248-258. https://doi.org/10.1176/appi.ajp.164.2.248