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Submitted:
09 February 2023
Posted:
09 February 2023
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Study and year of publication | Candidate gene(s) and polymorphisms studied | Study design | Study population and sample size | Results | Study quality (Q-Genie quality score) |
---|---|---|---|---|---|
Comings et al., 1991 [34] | DRD2 (Taq1 SNP) | Single-gene association | Patients seeking psychiatric care, Caucasian (n = 314) | DRD2 Taq1 A1 allele not significantly associated with depression or obesity | Poor (31) |
Comings et al., 1996 [35] | Ob (D7S1875 repeat polymorphism) | Single-gene association | Young adults (age 26-30), Caucasian (n = 208) | Ob D7S1875 <208bp repeat polymorphism significantly associated with BMI and depressive symptoms, but only in women | Moderate (42) |
Ejchel et al., 2005 [36] | APOA4 (360 Gln/His SNP) | Single-gene association | Elderly adults (age ≥ 60) (n = 383) | APOA4 360 His allele associated with both obesity and depression | Moderate (39) |
Chen et al., 2006 [37] |
APOA5 (-1131T→C SNP) |
Single-gene association | Elderly adults (age 66-97) (n = 371) | APOA5 -1131 C allele associated with obesity in the presence of depression | Moderate (37) |
Krishnamurthy et al., 2008 [38] | NR3C1 (Bcl1, N363S, rs33388 and rs33389 SNPs) | Single-gene association | Premenopausal women (age 21-45) with (n = 52) and without (n = 29) depression | NR3C1 Bcl1 G/G genotype associated with greater abdominal obesity in women with depression; no significant association for other SNPs | Moderate (39) |
Spalova et al., 2008 [39] | NMB (P73T SNP) | Single-gene association | Adults with (n = 292) and without (n = 155) obesity or overweight, Caucasian | No significant effect of NMB P73T on weight loss or depressive symptoms when followed up over 2.5 years after a weight reduction programme | Moderate (42) |
Fuemmeler et al., 2009 [40] | MAOA (30 bp VNTR) and SLC6A4 (5-HTTLPR 44bp Ins/Del) | Multiple-gene association, gene x depression interaction | Adolescents (n = 1584) | MAOA high-activity variant associated with lower risk of obesity in the presence of depression in male but not female adolescents | Moderate (45) |
Kivimaki et al., 2011 [41] | FTO (rs1421085 SNP) | Single-gene association | Adults (age 35-55) (n = 4145) | FTO rs1421085 C allele associated with depression and obesity in men, but not in women; link between risk allele and depression in men apparently independent of obesity | Good (48) |
Rivera et al., 2012 [42] | FTO (10 SNPs) | Single-gene association; gene x depression interaction | Two independent samples of adults with (n = 3734) and without (n = 2499) major depression | Significant associations between 5 SNPs of FTO and BMI in adults with depression, but not in controls | Good (55) |
Samaan et al., 2013 [43] | FTO (rs9939609 SNP) | Single-gene association | Pooled data from 4 samples of adults with (n = 6561) and without (n = 21932) depression | FTO rs993609 A variant associated with increased BMI but lower risk of depression | Good (53) |
Beydoun et al., 2014 [44] | 21 SNPs across 10 genes (ABCG5, APOB, APOA4, APOE, BCMO1, CD36, LIPC, FABP2, LPL, SCARB1) associated with serum carotenoid levels | Multiple-gene association study | Adults (age 30-64), African-American (n = 873) | No specific association between any individual SNP and either obesity or depression | Good (49) |
Harbron et al., 2014 [45] | FTO (rs1421085 and rs17817449 SNPs and haplotype) | Single-gene association; gene x depression interaction | Adults with obesity, Caucasian (n = 133) | FTO rs17817449 GG genotype associated with more severe depressive symptoms; rs1421085 C allele mediates relationship between depressive symptoms and BMI | Moderate (41) |
Bielinski et al., 2015 [46] | SLC6A4 (44-bp Ins/Del) and HTR2A (1438G/A SNP) | Multiple-gene association | Adults (age 18-73) with obesity, Caucasian (n = 180) | No significant association between either variant and depressive symptoms | Moderate (43) |
Borkowska et al., 2015 [47] | SLC6A4 (5-HTTLPR repeat polymorphism) | Single-gene association | Adults with obesity, Caucasian (n = 390) | 5-HTTLPR L/L genotype associated with higher BMI and more severe depressive symptoms | Good (47) |
Delacretaz et al., 2015 [48] | MCHR2 (8 SNPs) and MCHR2-AS1 (4 SNPs) | Multiple-gene association | Independent analyses of Caucasian adults with psychiatric disorders (n = 816) and in the general population (n = 119218) | MCHR2 rs7754794 TT genotype associated with lower BMI in patients with depression; similar but weaker association observed in the general population | Good (57) |
McCaffery et al., 2015 [49] | 8 SNPs at 6 loci previously associated with depressive symptoms | Multiple-gene association | Adults with obesity or overweight, multi-ethnic (n = 2118) | KCNE1 rs1543654 associated with depressive symptoms; no significant associations for other SNPs | Good (46) |
Samaan et al., 2015 [50] | 21 SNPs previously associated with obesity | Multiple-gene association | Multi-ethnic adults with (n = 3209) and without (n = 14195) depression | TAL1 rs2984618 SNP significantly associated with both BMI and major depression | Good (53) |
Yilmaz et al., 2015 [51] | MC4R (rs571312, rs17782313, rs489693, rs11872992 and rs8087522 SNPs) | Single-gene association | Adults (age 24-50), Caucasian (n = 328) | MC4R rs17782313 C allele associated with higher depressive symptoms and higher BMI, but the latter was not significant after correction | Good (51) |
Quteineh et al., 2016 [52] | CRTC1 (rs3746266 and rs6510997 SNPs) | Single-gene association | Pooled data from 3 samples of adults with (n = 5344) and without (n = 5515) major depression | No overall association between CRTC1 polymorphisms and depression; CRTC1 rs3746266 G allele and rs6510997 C allele associated with BMI in one of the samples | Moderate (43) |
Bielinski et al., 2017 [53] | COMT (Val158Met) and DAT1 (VNTR polymorphism) | Multiple-gene association | Adults (age 39-69) with obesity, Caucasian (n = 364) | DAT1 9-repeat allele associated with higher BMI and depressive symptoms; COMT Met/Met genotype associated with depressive symptoms | Moderate (42) |
Hellgren et al., 2017 [54] | 38 SNPs of four genes (AKR1C2, AKR1C4, SRD5A1 and SRD5A2) involved in allopregnanolone synthesis | Multiple-gene association | Pregnant women, Caucasian (n = 1351) | AKR1C2 rs28488494 SNP associated with BMI; AKR1C2 rs1937863 SNP associated with postnatal depressive symptoms | Good (50) |
Rivera et al., 2017 [55] | FTO (rs9939609 SNP) | Single-gene association; gene x depression interaction | Pooled data from 5 samples of adults with (n = 6902) and without (n = 6799) depression | FTO rs9939609 A variant associated with higher BMI in patients with depression but not in controls | Good (54) |
Schepers and Markus, 2017 [56] | SLC6A4 (5-HTTLPR repeat polymorphism) | Single-gene association | Healthy young adults (mean age 21.3) (n = 827) | 5-HTTLPR S allele associated with higher BMI and depressive symptoms | Moderate (45) |
Treutlein et al., 2017 [57] | NPY2R (rs6857715 SNP) | Single-gene association; gene x weight interaction | Adults with depression (n = 595) and general population controls (n = 1295) | NPY2R rs6857715 T allele associated with depression independent of increased weight; trend towards an association between T allele weight gain in depressed patients | Good (51) |
Brummett et al., 2018 [58] | HTR2C (rs6318 SNP) | Single-gene association | Pooled data from 10 adult samples, Caucasian and African-American (n = 27161) | No association between HTR2C rs6318 and either depressive symptoms or BMI | Good (54) |
Hay et al., 2022 [59] | PCSK9 and surrounding locus (7 lead SNPs identified through sequential analysis of biobank data) | Single-locus association | Data from adult Biobank samples, mixed ethnicity (n = 73627) | PCSK9 rs2647282 associated with BMI; no association between any PCSK9 SNP and major depression | Good (49) |
He et al., 2022 [60] | HTR2C (13 rare variants identified in a prior sample) | Single-gene association | Data from adult Biobank samples, Caucasian (n = 153352) | HTR2C V61I variant associated with depression and obesity, but not significant after correction | Moderate (44) |
Rahati et al., 2022 [61] | MC4R (rs17782313 SNP) | Single-gene association | Adults (age 20-50) with obesity or overweight, Iranian (n = 403) | MC4R rs17782313 C allele associated with higher depressive symptoms; CC genotype associated with higher body weight | Moderate (45) |
Genetic locus | Physiological effects of gene product | Impact on obesity and depression |
---|---|---|
Genes with replicated associations | ||
FTO (5 studies) | DNA/RNA demethylase enzyme that influences food intake, adiposity and energy expenditure | Multiple SNPs associated with elevated BMI in depression but not in general samples [42] rs9939609 A allele associated with higher BMI both in general samples and in patients with depression; also associated with lower depressive symptoms in general samples [43,55] rs17817749 GG genotype associated with elevated depressive symptoms in adults with obesity [45] rs1421085 C allele interacts with depressive symptoms to influence higher BMI [41] |
MC4R (2 studies) | G-protein coupled, membrane-bound receptor for α-melanocyte stimulating hormone | rs17782313 C allele associated with increased depressive symptoms in adults both with and without obesity [51] CC genotype associated with increased body weight in adults with obesity [61] |
Genes with positive findings in single studies | ||
AKR1C2 | Reduction of 5α-dihydroprogesterone to allopregnanolone; one of two isoforms expressed in the brain | rs28488494 associated with BMI and rs1937863 associated with post-partum depressive symptoms in pregnant women [54] |
APOA5 | Component of high-density lipoprotein (HDL); involved in regulation of plasma triglyceride levels | -1131 C allele associated with obesity in elderly adults with depression [37] |
COMT | O-methylation and inactivation of catecholamine neurotransmitters – dopamine, epinephrine, norepinephrine | rs4680 Met/Met genotype associated with depressive symptoms in adults with obesity [53] |
DAT1 | Reputake of dopamine into presynaptic neurons | 9-repeat allele associated with higher BMI and elevated depressive symptoms [53] |
KCNE1 | Regulation of voltage-gated potassium channel activity in cardiac muscle, inner ear and brain | rs1543654 associated with depressive symptoms in adults with obesity [49] |
MAOA | Catabolism of monoamine neurotransmitters – dopamine, serotonin, norepinephrine | High-activity variant associated with reduced obesity in adolescent girls with depression [40] |
MCHR2 | G-protein coupled, membrane-bound receptor for melanin concentrating hormone | rs7754794 TT genotype associated with lower BMI in patients with depression [48] |
NPY2R | Receptor for neuropeptide Y, which is involved in the stress response, eating behaviour, cognition and pain perception | rs6857715 T allele associated with depression independent of BMI [57] Trend towards an association between this allele and increased BMI in patients with depression [57] |
NR3C1 | Nuclear receptor for cortisol and other glucocorticoid hormones; involved in regulation of carbohydrate metabolism, immune-inflammatory activity and the stress response | Bcl1 G/G genotype associated with greater obesity in women with depression [38] |
Ob (Leptin) | Centrally active hormone secreted by adipose cells; regulates satiety and energy expenditure | D7S1875 <208bp variant associated with depressive symptoms and higher BMI in women [35] |
PCSK9 | Proprotein convertase enzyme; regulates serum cholesterol levels by modulating the number of low-density lipoprotein receptors (LDL) | rs2647282 associated with BMI in adults; no association with depression [59] |
TAL1 | Transcription factor involved in differentiation of erythroid and myeloid cells | rs2984618 associated with higher BMI and risk of major depression in adults [50] |
Genes with mixed positive and negative findings | ||
SLC6A4a | Reputake of serotonin into presynaptic neurons | 5-HTTLPR s allele associated with higher BMI and depressive symptoms in young adults [56] 5-HTTLPR l/l genotype associated with higher BMI and more severe depressive symptoms in adults with obesity [47] |
APOA4b | Component of very low-density lipoprotein (VLDL) and chylomicrons; activator of enzymes involved in lipid metabolism; involved in regulation of serum cholesterol levels | 360 Gln/His associated with obesity and depression in elderly adults [36] |
Target gene | Synthetic agents | Natural agents |
---|---|---|
FTO | Selective inhibitors of FTO demethylasea |
Angelica sinensis ext. Rhein |
MC4R | Bremelanotideb Setmelanotideb |
Moringa oleifera ext. Daisaikoto |
AKR1C2 | Selective ARK1C2 inhibitorsa | Astaxanthin Bai He Gun Jin Tiang |
KCNE1 | - |
Coriandrum sativum ext. Gintoin Rottlerin |
MCHR2 | GW803430a | - |
NPY2R | Neuropeptide Y, intranasala Combined NPY2R and GLP-1 agonistsa |
Panax ginseng ext. |
NR3C1 | CORT125281a PT150c |
Aesculus turbinata ext. Curcumin Baihe Zhimu Xingpi Jieyu |
Ob | - |
Commiphora myrrha ext. Nelumbo nucifera ext. Prunus persica ext. |
PCSK9 | Alirocumabb Evolocumabb |
Lysimacha vulgaris ext. Protium heptaphyllum ext. Salvia plebeia ext. |
TAL1 | PIK-75a | - |
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