1. ¹Genetic-Epidemiology Unit, Departments of Epidemiology and Biostatistics and Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
2. ²Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands
3. ³Department of Molecular Genetics, Applied Molecular Genomics Group, VIB, University of Antwerp, Antwerp, Belgium
4. ⁴Department of Psychiatry, University of Leuven, Leuven, Belgium

Correspondence: Professor CM van Duijn, Department of Epidemiology and Biostatistics, Erasmus University Medical Center, PO Box 2040, Rotterdam 3000 CA, The Netherlands. E-mail: c.vanduijn@erasmusmc.nl

Received 27 February 2007; Revised 9 August 2007; Accepted 10 August 2007; Published online 16 October 2007.

Abstract

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 2 (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).