A genome-wide screen for depression in two independent Dutch populations.
BACKGROUND
Depression has a strong genetic component but candidate gene studies conducted to date have not shown consistent associations.


METHODS
We conducted a genome-wide parametric and nonparametric linkage analysis in a large-scale family-based study including 115 individuals with depression who were identified based on the Hospital Anxiety Depression Scale, Center for Epidemiologic Studies Depression Rating Scale, or use of antidepressive medication. Further, we investigated the most promising chromosomal regions found in the genome-wide linkage analysis with an association analysis in 734 individuals in the family-based study and 2373 individuals in the population-based study.


RESULTS
Our study demonstrated evidence for significant linkage of depression to chromosome 2p16.1-15 (logarithm of odds [LOD] = 5.13; parametric analysis) and suggestive evidence for linkage in nonparametric analysis to chromosome 5p15.33 (LOD = 2.14), 11q25 (LOD = 2.27), and 19p13.3 (LOD = 2.66). The subsequent association analysis in the family-based study showed region-wide significant association in intron 1 of the OPCML gene on chromosome 11q25 (empirical p value = .04). The association analysis in the population-based study did not show any region-wide significant association, yet showed suggestive association in intron 1 of the APLP2 gene on chromosome 11q25.


CONCLUSIONS
Our linkage and association studies suggest a locus for depression on chromosomes 2p16.1-15 and 11q25. The linkage to chromosome 11q25 may be, in part, explained by the OPCML or the APLP2 gene. Further, there is evidence for a role of the GNG7 gene (chromosome 19p13.3).
Schol-Gelok
Suzanne
S
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Janssens
A Cecile J W
AC
Tiemeier
Henning
H
Liu
Fan
F
Lopez-Leon
Sandra
S
Zorkoltseva
Irina V
IV
Axenovich
Tatiana I
TI
van Swieten
John C
JC
Uitterlinden
André G
AG
Hofman
Albert
A
Aulchenko
Yurii S
YS
Oostra
Ben A
BA
van Duijn
Cornelia M
CM
D000368:Aged; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009426:Netherlands