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


METHODS
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.
Holmans
Peter
P
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 701A Welch Rd., Suite 3325, Palo Alto, CA 94304-5797, USA.
Weissman
Myrna M
MM
Zubenko
George S
GS
Scheftner
William A
WA
Crowe
Raymond R
RR
Depaulo
J Raymond
JR
Knowles
James A
JA
Zubenko
Wendy N
WN
Murphy-Eberenz
Kathleen
K
Marta
Diana H
DH
Boutelle
Sandra
S
McInnis
Melvin G
MG
Adams
Philip
P
Gladis
Madeline
M
Steele
Jo
J
Miller
Erin B
EB
Potash
James B
JB
Mackinnon
Dean F
DF
Levinson
Douglas F
DF
D000328:Adult; D017668:Age of Onset; D002874:Chromosome Mapping / Q000706:statistics & numerical data*; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015897:Comorbidity; D004276:DNA, Satellite / Q000235:genetics; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010551:Personality / Q000235:genetics; D012008:Recurrence
D004276:DNA, Satellite; D005819:Genetic Markers