Retinoid-related orphan receptor alpha (RORA) gene variation is associated with trait depression

Ming, Qingsen; Wang, Xiang; Chai, Qiaolian; Yi, Jinyao; Yao, Shuqiao

doi:10.1016/j.psychres.2015.07.014

Cited by 7 publications

(9 citation statements)

References 5 publications

(6 reference statements)

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“…The protein encoded by this gene has been shown to interact with NM23-1, which is the product of a tumor metastasis suppressor candidate gene 22 , 23 . It has been associated with diseases such as atrial tachyarrhythmia with short PR interval and trait depression 22 , 24 – 26 . Li and colleagues 27 conducted a molecular mapping of a developing dorsal horn by microarray.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer

Reyes‐Gibby

Wang

Yeung

et al. 2018

Sci Rep

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Neuropathic pain (NP), defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system, is a debilitating chronic pain condition often resulting from cancer treatment. Among cancer patients, neuropathy during cancer treatment is a predisposing event for NP. To identify genetic variants influencing the development of NP, we conducted a genome-wide association study in 1,043 patients with squamous cell carcinoma of the head and neck, based on 714,494 tagging single-nucleotide polymorphisms (SNPs) (130 cases, 913 controls). About 12.5% of the patients, who previously had cancer treatment, had neuropathy-associated diagnoses, as defined using the ICD-9/ICD-10 codes. We identified four common SNPs representing four genomic regions: 7q22.3 (rs10950641; SNX8; P = 3.39 × 10−14), 19p13.2 (rs4804217; PCP2; P = 2.95 × 10−9), 3q27.3 (rs6796803; KNG1; P = 6.42 × 10−9) and 15q22.2 (rs4775319; RORA; P = 1.02 × 10−8), suggesting SNX8, PCP2, KNG1 and RORA might be novel target genes for NP in patients with head and neck cancer. Future experimental validation to explore physiological effects of the identified SNPs will provide a better understanding of the biological mechanisms underlying NP and may provide insights into novel therapeutic targets for treatment and management of NP.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer

Reyes‐Gibby

Wang

Yeung

et al. 2018

Sci Rep

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“…Genes candidates were selected based on previous data implicating an association with the studies SNPs and clinical syndrome of depression [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]; anxiety [42][43][44] or stress [45] diagnosed according to Diagnostic and Statistical Manual of Mental Disorders and/or International Statistical Classification of Diseases. The genotyping analysis of candidate genes polymorphism was analyzed using Agene ® MassARRAY platform.…”

Section: Mass Array Genotypingmentioning

confidence: 99%

“…These genes may be associated with depression or anxiety; however, there are ample studies which have failed to replicate the same results in the candidate gene literature [29][30][31]. One explanation for this lack of success in producing the replicable main effect of these genes is that the certain genetic variants are highly dependent on the gender, population, and disease-related outcomes [32]; even though these studies have recruited patients with major depressive disorder [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41]; anxiety disorder [42][43][44]; and post-traumatic stress disorders [45] diagnosed according to Diagnostic and Statistical Manual of Mental Disorders and/or International Statistical Classification of Diseases. This has led to increasing skepticism about the true association or lack thereof between candidate genes and psychological symptoms of depression, anxiety and/or stress.…”

Section: Introductionmentioning

confidence: 99%

“…To this end, we have constructed a custom of SNP array containing 18 genes that were chosen based on hypotheses regarding biological systems of relevance to depression [46][47][48][49][50]; anxiety [42,51,52] and stress [45,53]. These custom SNPs provide excellent coverage of many previously suggested and functionally important candidate genes for depression, anxiety and stress, including NPY5R [42,52]; ANO2 [42]; EPHX2 [42,51]; TPH2 [35]; NRG1 [34]; LHPP [38,39,54]; FKBP5 [41,45]; SDK2 [42]; RORA [33,55]; OXTR [27,28]; BDNF [56,57]; HTR2C [43]; TEX51 [42]; and PLEKHG1 [42]. Many of the genes represented on the array have also been reported to be involved in associated heritable phenotypes that are associated with symptoms of depression, anxiety and/or stress.…”

Section: Introductionmentioning

confidence: 99%

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Association Analysis of 14 Candidate Gene Polymorphism with Depression and Stress among Gestational Diabetes Mellitus

Lee

Ching

Ramachandran

et al. 2019

Genes

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The association of candidate genes and psychological symptoms of depression, anxiety, and stress among women with gestational diabetes mellitus (GDM) in Malaysia was determined in this study, followed by the determination of their odds of getting psychological symptoms, adjusted for socio-demographical background, maternal, and clinical characteristics. Single nucleotide polymorphisms (SNPs) recorded a significant association between SNP of EPHX2 (rs17466684) and depression symptoms (AOR = 7.854, 95% CI = 1.330-46.360) and stress symptoms (AOR = 7.664, 95% CI = 1. 579-37.197). Associations were also observed between stress symptoms and SNP of OXTR (rs53576) and (AOR = 2.981, 95% CI = 1.058-8.402) and SNP of NRG1 (rs2919375) (AOR = 9.894, 95% CI = 1.159-84.427). The SNP of EPHX2 (rs17466684) gene polymorphism is associated with depression symptoms among Malaysian women with GDM. SNP of EPHX2 (rs17466684), OXTR (rs53576) and NRG1 (rs2919375) are also associated with stress symptoms.

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“…RORα is implicated in neuropsychiatric disorders including autism spectrum disorders (ASD), bipolar disorder (BD) and major depressive disorder (MDD) [29][30][31][32][33][34][35][36][37][38][39][40]. Specifically, neuroanatomical abnormalities in patients with autism including loss of Purkinje cells, reduced cerebellar volume and interrupted cerebello-thalamo-cortical pathways resembles that of staggerer mice [41].…”

Section: Introductionmentioning

confidence: 99%

Loss of RAR-related orphan receptor alpha (RORα) selectively lowers docosahexaenoic acid in developing cerebellum

Chen

Schultz

Haven

et al. 2020

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Deficiency in retinoid acid receptor-related orphan receptor alpha (RORα) of staggerer mice results in extensive granule and Purkinje cell loss in the cerebellum as well as in learned motor deficits, cognition impairments and perseverative tendencies that are commonly observed in autistic spectrum disorder (ASD). The effects of RORα on brain lipid metabolism associated with cerebellar atrophy remain unexplored. The aim of this study is to examine the effects of RORα deficiency on brain phospholipid fatty acid concentrations and compositions. Staggerer mice (Rora sg/sg) and wildtype littermates (Rora +/+) were fed n-3 polyunsaturated fatty acids (PUFA) containing diets ad libitum. At 2 months and 7 or more months old, brain total phospholipid fatty acids were quantified by gas chromatography-flame ionization detection. In the cerebellum, all fatty acid concentrations were reduced in 2 months old mice. Since total fatty acid concentrations were significantly different at 2-monthold, we examined changes in fatty acid composition. The composition of ARA was not significantly different between genotypes; though DHA composition remained significantly lowered. Despite cerebellar atrophy at >7months-old, cerebellar fatty acid concentrations had recovered comparably to wildtype control. Therefore, RORα may be necessary for fatty acid accretions during neurodevelopment. Specifically, the effects of RORα on PUFA metabolisms are region-specific and age-dependent.

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Retinoid-related orphan receptor alpha (RORA) gene variation is associated with trait depression

Cited by 7 publications

References 5 publications

Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer

Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer

Association Analysis of 14 Candidate Gene Polymorphism with Depression and Stress among Gestational Diabetes Mellitus

Loss of RAR-related orphan receptor alpha (RORα) selectively lowers docosahexaenoic acid in developing cerebellum

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