Table 2.
Genetic Variant and Poly- morphism |
Findings | Sample size |
Mood Disorders |
Correc- tions |
Gene coverage |
Subject criteria |
Study type & phenotype definition |
Fin- dings |
References |
---|---|---|---|---|---|---|---|---|---|
P2X7 | |||||||||
P2X7: rs2230912 Gln460Arg |
Not associated with diagnosis. BD subjects with at least one allele had higher symptom severity | 315 | BD and MDD | Bonferroni; adjusted for gender on HADS | GWAS (assessed multiple genotypes) | DSM-IV by psychiatrists | Case-control, symptom severity (MADRS and HDRS scores) | +/− | (Halmai et al., 2013) |
Associated with length of current mood episode, which was moderated by neurotic traits | 424 | BD and MDD | Based on (Soronen et al., 2011) | Based on (Soronen et al., 2011); gene specific | Semi-structured interview | Length of episode moderated by neurotic traits | + | (Mantere et al., 2012) | |
Associated with rapid cycling BD diagnosis | 690 (n=569 BD-I, n=121 rapid cycling) | BD only | Correction by permutation tests; gender-confounder adjusted | 3 SNPs | Lifetime assessment for specific symptoms, medical records, and interviews | Manic symptoms, then case-case | + | (Backlund et al., 2011) | |
|
450 (n=178 BD, n=272 MDD) | BD and MDD | Gender and age adjustment | Specific allelic association analyses | Semi-structured interview | Case-control, post-hoc by diagnosis, family history, duration of illness | + | (Soronen et al., 2011) | |
|
457 | Depression (including MDD, dysthymia, and mixed anxiety depression) | Adjusted for gender and age | Specific allelic association analysis | DSM-IV by MDI | Case-control; multiple scales (anxiety, obsessive- compulsive, depression, eating disorders, disability, alcohol abuse, well-being, environmental risks) | − | (Lavebratt et al., 2010) | |
Associated with diagnosis of BD | 604 | BD only | Not corrected | Specific allelic association analysis | Structured interview | Case-control | + | (McQuillin et al., 2009) | |
Associated with increased symptom severity (both depression and anxiety) in both BD and MDD | 171 | BD and MDD | Adjusted for gender and age | Specific allelic association analysis | DSM-IV | Case control, then symptom severity (HADS) | + | (Hejjas et al., 2009) | |
Not associated with diagnosis | 1445 (European cohort) | BD and MDD | Corrected by permutations | Single marker association analysis | Structured interview | Case-control | − | (Grigoroiu-Serbanescu et al., 2009) | |
Not associated with diagnosis | 1723 (n=687 BD, n=1036 MDD) | BD and MDD | Bonferroni; adjusted for gender and age | Specific allelic association analysis | DSM-IV and semi-structured interview | Case-control, familial study | − | (Green et al., 2009) | |
Associated with increased symptom severity | 218 | Diabetics with mixed symptoms of anxiety and depression | False discovery rate correction | Specific allelic association analysis | Symptoms assessed by HADS | Case-case, symptom severity | + | (Nagy et al., 2008) | |
Associated with diagnosis of depression | 1000 | MDD only | False discovery rate correction, then correction by permutation | Specific allelic association analysis | DSM-IV and semi-structured interview | Case-control | + | (Lucae et al., 2006) | |
Associated with diagnosis of BD | 485 | BD only | Adjusted p-value in stats package vs. expected frequency of alleles | Specific allelic association analysis, linkage analysis | Structured interview | Case-control, familial study | + | (Barden et al., 2006) | |
P2X7: rs208294 His155Tyr |
|
450 | BD and MDD | Adjusted for gender and age | Specific allelic association analysis | Semi-structured interview | Case-control, post-hoc by diagnosis, family history, duration of illness | + | (Soronen et al., 2011) |
|
613 (n=218 with MDD) | MDD only | Adjusted for gender and age | Specific allelic association analyses | DSM-IV, MADRS | Case-control, Case-case, MADRS score change | − | (Viikki et al., 2011) | |
P2X7: rs171811 Thr348Ala |
Associated with symptoms of cognitive impairment, distractibility, talkativeness, and thought disorder | 690 | BD only | Correction by permutation tests, adjusted for gender | 3 SNPs | Lifetime assessment for specific symptoms, medical records, and interviews | Case-case by manic symptoms | + | (Backlund et al., 2011) |
Trend towards an association with symptom severity for panic and agoraphobia | 179 pts, 462 controls | Anxiety disorders (including panic disorder and agoraphobia) | Correction by permutation tests, adjusted for gender | 25 SNPs | Structured interviews | Case-control, symptom severity by panic and agoraphobia scale | ~ | (Erhardt et al., 2007) | |
P2X7: rs1653625 AA (not AC or CC) in the 3′ un- translated region of the P2RX7 gene |
|
315 (n=195 MDD, n=120 BD) | BD and MDD | Bonferroni and adjusted for gender on HADS | GWAS (assessed multiple genotypes) | DSM-IV by psychiatrists | Case-control, symptom severity (MADRS and HDRS score) | −/~ | (Halmai et al., 2013) |
Other Purinergic SNPs | |||||||||
A2aAR: 1976C/T A2A receptor |
Not associated with a mood disorder diagnosis | 192 patients (408 total) | BD and MDD | No | Single marker association analysis | DSM-IV criteria | Case-control | − | (Tsai et al., 2006) |
Not associated with a diagnosis of panic disorder | 104 pts, 192 controls (Chinese cohort) | Panic disorder | No | Single marker association analysis | Semi- structured interview | Case-control | − | (Lam et al., 2005) | |
Associated with symptoms of panic disorder and agorophobia | 70 subjects from pedigree, 83 familialtrios | Panic disorder | No | Haplotype combinations of 14 SNPs | Semi-structured interview | Familial pedigree study, panic disorder and agoraphobia scale | + | (Hamilton et al., 2004) | |
Associated with greater anxiety after caffeine challenge (also with the 2592T/T A2A receptor SNP) | 100 | No mood disorder history | No | 4 loci of the A2A receptor | Telephone and in person screen | All healthy, double-blind study | + | (Alsene et al., 2003) | |
Mito-chondrial DNA 5178 |
|
145 patients, 184 controls | BD only | No | Single marker association analysis | DSM-IV by two psychiatrists | Case-control | + | (Kato et al., 2000) |
SLC29A3, rs12256138 Variation in nucleoside (including adenosine) transporter gene transport |
Associated with a diagnosis of depression or sleep disturbance | 1423 (cohort of Finnish women) | MDD and symptoms of sleep disturbance | Bonferroni and adjusted for gender | 117 SNPs from 13 genes | Structured interview | Case-control | + | (Gass et al., 2010) |
GNB3, C825T poly-morphism G-protein B3 subunit |
Associated with antidepressant response | Meta-analysis | Depression (varied) | Varied | Single marker association analysis | Varied | Varied | + | (Klenke et al., 2011) |
indicates a positive association between the SNP and disease risk or a related phenotype
indicates no association between the SNP and disease risk or a related phenotype
Trend towards an association between the SNP and disease risk or a related phenotype
Abbreviations: BD: bipolar disorder; MDD: major depressive disorder; SNP: single nucleotide polymorphism; HDRS: Hamilton Depression Rating Scale, MADRS: Montgomery-Asberg Depression Rating Scale; MDI: Major Depressive Inventory; HADS: Hospital Anxiety and Depression Scale; GWAS: genome-wide association study; SSRI: selective serotonin reuptake inhibitor; ECT: electroconvulsive therapy.