Genome-wide association study of major recurrent depression in the U.K. population.
OBJECTIVE
Studies of major depression in twins and families have shown moderate to high heritability, but extensive molecular studies have failed to identify susceptibility genes convincingly. To detect genetic variants contributing to major depression, the authors performed a genome-wide association study using 1,636 cases of depression ascertained in the U.K. and 1,594 comparison subjects screened negative for psychiatric disorders.


METHODS
Cases were collected from 1) a case-control study of recurrent depression (the Depression Case Control [DeCC] study; N=1346), 2) an affected sibling pair linkage study of recurrent depression (probands from the Depression Network [DeNT] study; N=332), and 3) a pharmacogenetic study (the Genome-Based Therapeutic Drugs for Depression [GENDEP] study; N=88). Depression cases and comparison subjects were genotyped at Centre National de Génotypage on the Illumina Human610-Quad BeadChip. After applying stringent quality control criteria for missing genotypes, departure from Hardy-Weinberg equilibrium, and low minor allele frequency, the authors tested for association to depression using logistic regression, correcting for population ancestry.


RESULTS
Single nucleotide polymorphisms (SNPs) in BICC1 achieved suggestive evidence for association, which strengthened after imputation of ungenotyped markers, and in analysis of female depression cases. A meta-analysis of U.K. data with previously published results from studies in Munich and Lausanne showed some evidence for association near neuroligin 1 (NLGN1) on chromosome 3, but did not support findings at BICC1.


CONCLUSIONS
This study identifies several signals for association worthy of further investigation but, as in previous genome-wide studies, suggests that individual gene contributions to depression are likely to have only minor effects, and very large pooled analyses will be required to identify them.
Lewis
Cathryn M
CM
Medical Research Council's Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, London, United Kingdom. cathryn.lewis@kcl.ac.uk
Ng
Mandy Y
MY
Butler
Amy W
AW
Cohen-Woods
Sarah
S
Uher
Rudolf
R
Pirlo
Katrina
K
Weale
Michael E
ME
Schosser
Alexandra
A
Paredes
Ursula M
UM
Rivera
Margarita
M
Craddock
Nicholas
N
Owen
Mike J
MJ
Jones
Lisa
L
Jones
Ian
I
Korszun
Ania
A
Aitchison
Katherine J
KJ
Shi
Jianxin
J
Quinn
John P
JP
Mackenzie
Alasdair
A
Vollenweider
Peter
P
Waeber
Gerard
G
Heath
Simon
S
Lathrop
Mark
M
Muglia
Pierandrea
P
Barnes
Michael R
MR
Whittaker
John C
JC
Tozzi
Federica
F
Holsboer
Florian
F
Preisig
Martin
M
Farmer
Anne E
AE
Breen
Gerome
G
Craig
Ian W
IW
McGuffin
Peter
P
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012008:Recurrence; D006113:United Kingdom / Q000453:epidemiology
D005819:Genetic Markers