Investigations of polymorphisms in sex steroid receptor genes in relation to psychiatric disorders and behaviour
| Gene | Polymorphism | Trait | No. of patients; (M/F) | No. of subjects or control subjects; (M/F) | Ethnicity | Main finding | Study |
|---|---|---|---|---|---|---|---|
| AR | CAG/GGC repeats | Tourette syndrome, ADHD and conduct disorder scores | 250 (202/48) | 52 (19/33) | White | Individuals with long CAG and long GGC had lower ADHD, CD, ODD scores. | Comings et al.15 |
| AR | CAG/GGC repeats | Personality (TCI) | 204 (204/0) | White | Individuals with long CAG or long GGC had higher self-transcendence scores. | Comings et al.16 | |
| AR | GGC repeat | Measures of aggression, hostility (Buss–Durkee Inventory, DSQ, TCI, LOC, sexual habits in men, parental divorce and age of menarche in women. | 285 (121/164) | White | In men, the presence of the 16 repeat allele of the GGC was associated with traits related to aggression, hostility and impulsivity, as well as with sexual compulsions and the lifetime number of sex partners. In women, homozygosity for the 16 repeat allele was associated with divorce of parents, absent father and earlier age of menarche. | Comings et al.17 | |
| AR | GGC repeat | Adverse childhood experiences | 1702 (794/908) | White | No associations. | Jorm et al.18 | |
| AR | CAG repeat | Eysenck psychoticism | Adults: 588 (0/588) Adolescents: 912 (457/455) | White | Weak associations between short CAG repeats and high psychoticism scores in women, and low psychoticism scores in adolescent boys. | Loehlin et al.19 | |
| AR | CAG/GGC repeats | Eysenck psychoticism | 1698 (793/905) | White | Short CAG repeats associated with high psychoticism in men. | Turakulov et al.20 | |
| AR | CAG repeat | Personality (KSP) | 340 (186/154) | White | Long CAG repeats associated with high scores for Muscular Tension and Lack of Assertiveness. No associations after correction for multiple testing. | Jönsson et al.21 | |
| AR | CAG repeat | Antisocial behavioural traits | 2096 (1007/1089) | White | Men with medium CAG repeat lengths scored higher for antisocial traits. | Prichard et al.22 | |
| AR | CAG repeat | Schizophrenia | 225 (108/117) | 247 (125/122) | Chinese | No associations. | Tsai et al.23 |
| AR | CAG repeat | Violent criminal activity | 146 (146/0) | 108 (108/0) | Chinese | No association between the AR repeat length and violent convicts. More violent/criminal cases than control cases carried a short CAG repeat polymorphism. | Cheng et al.24 |
| AR | Mutation screen | Alcoholism, social phobia, schizophrenia, bipolar disorder, ADHD, autism | 173 | R726L was found in 1 of 17 scanned alcoholics, and P516S was identified in 1 of 3 phobia patients. | Yan et al.25 | ||
| AR | CAG repeat | Depression | 1000 (1000/0) | 958 white | Men with low total testosterone levels and short CAG repeats had increased risk for depression. | Seidman et al.26 | |
| AR | CAG repeat | Depression | 1246 (1246/0) | 525 black, 721 white | Interactive effect of CAG repeat length and testosterone levels on depressive symptoms. | Colangelo et al.27 | |
| AR | CAG repeat | Depression | 266 (266/0) | No associations. | T Sjoen et al.28 | ||
| AR | CAG repeat | Depression | 102 (0/102) | 150 (0/150) | Chinese | Female adolescent patients with depression had shorter mean CAG repeat length than control subjects. | Geng et al.29 |
| ESR1 | 16 SNPs of ESR1; COMT Val/Met | PMDD | 91 (0/91) | 56 (0/56) | White | 4 SNPs in intron 4 were associated with PMDD. The significant associations were only seen in carriers of the COMT Val/Val genotype. | Huo et al.30 |
| ESR1 | TA repeat | Personality (SCL-90) | 179 (179/0) | Mainly white | Individuals homozygous for the long TA repeat displayed higher anxiety scores. | Comings et al.31 | |
| ESR1 | PvuII, XbaI | Schizophrenia | 125 (50/75) | 142 (60/82) | Chinese | No associations. | Ouyang et al.32 |
| ESR1 | PvuII, XbaI | Bipolar disorder, puerperal psychosis | 219 (92/127) | 219 (94/125) | White | No associations. | Jones et al.33 |
| ESR1 | Mutation screen | Schizophrenia, bipolar disorder, puerperal psychosis, autism, ADHD, alcoholism | 240 | White | 3 missense mutations (H6Y, K299R, P146Q) were found in 1 patient each with bipolar disorder, puerperal psychosis and alcoholism. | Feng et al.34 | |
| ESR1 | Mutation screen | Bipolar disorder, puerperal psychosis | 231 (39/192) | 110 (38/72) | White | No association to the involvement of any of the rare ESR1 variants. | Middle et al.35 |
| ESR1 | PvuII, XbaI | MDD | 154 (65/89) | 226 (100/126) | Chinese | Pallele of the PvuII SNP was more frequent in female patients with depression compared with female control subjects. No association in men or in suicide attempters. | Tsai et al.36 |
| ESR1 | TA repeat | Personality (TCI) | 204 (204/0) | Mainly white | TA repeat length associated with personality traits. | Comings et al.37 | |
| ESR1 | TA repeat | Conduct disorder | 250 (202/48) | 52 (19/33) | Mainly white | TA repeat length associated with conduct disorder. | Comings et al.38 |
| ESR1 | TA repeat | Personality (KSP) | 172 (0/172) | White | A short TA repeat associated with higher anxiety and nonconformity scores. | Westberg et al.39 | |
| ESR1 | PvuII, XbaI, TA repeat | Personality (many different scales used) | 680 | White | 2-locus genotypes of the PvuII or XbaI SNPs and the TA repeat was associated with high anxiety scores in children and adolescents. | Prichard et al.40 | |
| ESR1 | TG repeat | Antisocial behavioural traits | 2096 (1007/1089) | White | Long TG repeat alleles were associated with higher scores for antisocial traits in men. Associations did not survive correction for multiple testing. | Prichard et al.22 | |
| ESR1 | PvuII, XbaI | Anxiety/depression | Anxiety: 2468 (1133/1335) Depression: 4098 (1694/2404) | White | An ESR1 haplotype was associated with anxiety in women, but not in men. No relation observed with depressive symptoms. | Tiemeier et al.41 | |
| ESR1 | PvuII, XbaI, TA repeat | Anorexia nervosa | 170 (0/170) | 152 (0/152) | White | No associations. | Eastwood et al.42 |
| ESR2 | 6 SNPs | PMDD | 91 (0/91) | 56 (0/56) | White | No associations. | Huo et al.30 |
| ESR2 | G1082A, A1730G, mutation screen | Anorexia nervosa, bulimia nervosa, obesity | Anorexia nervosa: 50 Bulimia nervosa: 28 Obesity: 96 | 25 | White | A 21 bp deletion (codons 238–244) was detected in 2 obese probands and an underweight individual. A 846G→A transition leading to a nonconservative amino acid substitution (G-250-S) was found in 2 obese male probands. 1082G allele was more frequent in anorexia nervosa patients. | Rosenkranz et al.43 |
| ESR2 | G1082A, A1730G | Anorexia nervosa | 170 (0/170) | 152 (0/152) | White | 1082A allele was more frequent in anorexia nervosa patients. | Eastwood et al.42 |
| ESR2 | G1082A; A1730G; cx+56 | Bulimic disease | 76 (0/76) | 60 (0/60) | White | 1730A and cx+56A alleles were more frequent in patients than in control subjects. A conserved mutation (R221G) was identified in 1 patient. | Nilsson et al.44 |
| ESR2 | CA repeat | Perimenopausal symptoms | 51 (0/51) | Japanese | The CA repeat length associated with menopausal problems such as vasomotor symptoms, psychological symptoms (including depressed mood) and premenstrual symptoms. | Takeo et al.45 | |
| ESR2 | CA repeat | Depression | 102 (0/102) | 150 (0/150) | Chinese | Patients had shorter mean ESR2 CA repeat length than control subjects. Short repeats were more prevalent in patients. No effects of ESR1 TA repeat. | Geng et al.29 |
| PGR | G331A | Panic disorder | 72 (24/48) | 452 (199/253) | White | 331A allele associated with panic disorder in women. | Ho et al.46 |
ADHD = attention-deficit hyperactivity disorder; AR = androgen receptor gene; CD = conduct disorder; COMT = catechol-O-methyltransferase gene; DSQ =Defense Style Questionnaire; ESR1 = estrogen receptor α gene; ESR2 = estrogen receptor β gene; F = female; KSP = Karolinska Scales of Personality; LOC = Locus of Control Test; M = male; MDD = major depressive disorder; ODD = oppositional defiant disorder; PGR = progesterone receptor gene; PMDD = premenstrual dysphoric disorder; SCL-90 = Symptom Checklist-90; SNP = single nucleotide polymorphism; TCI = Temperament and Character Inventory.