Meta-analyses of genetic studies on major depressive disorder.
The genetic basis of major depressive disorder (MDD) has been investigated extensively, but the identification of MDD genes has been hampered by conflicting results from underpowered studies. We review all MDD case-control genetic association studies published before June 2007 and perform meta-analyses for polymorphisms that had been investigated in at least three studies. The study selection and data extraction were performed in duplicate by two independent investigators. The 183 papers that met our criteria studied 393 polymorphisms in 102 genes. Twenty-two polymorphisms (6%) were investigated in at least three studies. Seven polymorphisms had been evaluated in previous meta-analyses, 5 of these had new data available. Hence, we performed meta-analyses for 20 polymorphisms in 18 genes. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Statistically significant associations were found for the APOE varepsilon2 (OR, 0.51), GNB3 825T (OR, 1.38), MTHFR 677T (OR, 1.20), SLC6A4 44 bp Ins/Del S (OR, 1.11) alleles and the SLC6A3 40 bpVNTR 9/10 genotype (OR, 2.06). To date, there is statistically significant evidence for six MDD susceptibility genes (APOE, DRD4, GNB3, MTHFR, SLC6A3 and SLC6A4).
López-León
S
S
Genetic-Epidemiology Unit, Department of Epidemiology and Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Janssens
A C J W
AC
González-Zuloeta Ladd
A M
AM
Del-Favero
J
J
Claes
S J
SJ
Oostra
B A
BA
van Duijn
C M
CM
D003865:Major Depressive Disorder / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D000099247:Taurine Transporters
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D000099247:Taurine Transporters; C493214:SLC6A3 protein, human