Predisposition locus for major depression at chromosome 12q22-12q23.2.
Major depression disorder is a common psychiatric disease with a major economic impact on society. In many cases, no effective treatment is available. The etiology of major depression is complex, but it is clear that the disease is, to a large extent, determined genetically, especially among individuals with a familial history of major depression, presumably through the involvement of multiple predisposition genes in addition to an environmental component. As a first step toward identification of chromosomal loci contributing to genetic predisposition to major depression, we have conducted a genomewide scan by using 628 microsatellite markers on 1,890 individuals from 110 Utah pedigrees with a strong family history of major depression. We identified significant linkage to major depression in males at marker D12S1300 (multipoint heterogeneity LOD score 4.6; P=.00003 after adjustment for multiple testing). With additional markers, the linkage evidence became highly significant, with the multipoint heterogeneity LOD score at marker D12S1706 increasing to 6.1 (P=.0000007 after adjustment for multiple testing). This study confirms the presence of one or more genes involved in psychiatric diseases on the q arm of chromosome 12 and provides strong evidence for the existence of a sex-specific predisposition gene to major depression at 12q22-q23.2.
Abkevich
Victor
V
Myriad Genetics, Salt Lake City, UT, 84108, USA. victor@myriad.com
Camp
Nicola J
NJ
Hensel
Charles H
CH
Neff
Chris D
CD
Russell
Deanna L
DL
Hughes
Dana C
DC
Plenk
Agnes M
AM
Lowry
Michael R
MR
Richards
R Lynn
RL
Carter
Catherine
C
Frech
Georges C
GC
Stone
Steven
S
Rowe
Kerry
K
Chau
Chi Ai
CA
Cortado
Kathleen
K
Hunt
Angelene
A
Luce
Karanina
K
O'Neil
Gayanne
G
Poarch
Jeff
J
Potter
Jennifer
J
Poulsen
Gregg H
GH
Saxton
Heidi
H
Bernat-Sestak
Michelle
M
Thompson
Victor
V
Gutin
Alexander
A
Skolnick
Mark H
MH
Shattuck
Donna
D
Cannon-Albright
Lisa
L
D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics*; D005820:Genetic Testing; D015894:Genome, Human; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D014589:Utah