A genome-wide multiphenotypic association analysis identified common candidate genes for subjective well-being, depressive symptoms and neuroticism

Chu, Xuan; Liu, Li; Wen, Yan; Li, Ping; Cheng, Bolun; Cheng, Shiqiang; Zhang, Lu; Ma, Mei; Qi, Xin; Liang, Chujun; Ye, Jing; Kafle, Om Prakash; Wu, Cuiyan; Wang, Sen; Xi, Wei; Ning, Yujie; Zhang, Feng

doi:10.1016/j.jpsychires.2020.02.012

Cited by 5 publications

(14 citation statements)

References 49 publications

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“…Of special interest were the associations with the symptoms measured by SCL-90R, particularly with depression, which showed two highly significant hits with MSRA haplotypes. This finding is in the same line as those by Chu et al, who recently published a GWAS reporting several MSRA variants related to depressive symptoms in the general population (Chu et al 2020). In this regard, the increase of reactive oxygen species (ROS) in the brain has been solidly connected with depression (Bhatt et al 2020).…”

Section: Discussionsupporting

confidence: 83%

“…There are, however, some examples in the general population that reveal associations between MSRA and symptoms that are relevant in ED. For example, several GWAS have identified MSRA variants solidly associated with irritability (Day et al 2016) and neuroticism (Okbay et al 2016;Luciano et al 2018;Chu et al 2020). Moreover, a replication study analyzing 16 features in over 140 000 participants also demonstrated significant effects of MSRA variants on neuroticism and extraversion (Boutwell et al 2017).…”

Section: Discussionmentioning

confidence: 99%

“…This gene is highly expressed in several areas of the brain and has in fact been related to several psychiatric conditions, such as schizophrenia (Walss-Bass et al 2009), bipolar disorder (Ni et al 2015) or Alzheimer's (Gabbita et al 1999) and Parkinson's disease (Wassef et al 2007), as well as being associated with a variety of behavioural traits and psychiatric symptoms (Reiterer et al 2019). In this regard, various genome-wide association studies (GWAS), replication studies, and meta-analyses (Day et al 2016;Fan et al 2017;Ma et al 2011;Amare et al 2018;Luciano et al 2018;Chu et al 2020) have shown that the occurrence of variability in the MSRA gene locus is likely behind the traits and psychiatric conditions observed.…”

Section: Introductionmentioning

confidence: 99%

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Variability in the antioxidant MSRA gene affects the psychopathology of patients with anorexia nervosa

González

García-Herráiz

Mota-Zamorano

et al. 2021

Acta Neuropsychiatr.

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Objective: To determine whether variability in the MSRA gene, related to obesity and several psychiatric conditions, may be relevant for psychopathological symptoms common in Anorexia Nervosa (AN) and/or for the susceptibility to the disorder. Methods: A total of 629 women (233 AN patients and 396 controls) were genotyped for 14 tag-SNPs. Psychometric evaluation was performed with the EDI-2 and SCL-90R questionnaires. Genetic associations were carried out by logistic regression controlling for age and adjusting for multiple comparisons (FDR method). Results: Two tag-SNPs, rs11249969 and rs81442 (with a pair-wise r2 value of 0.41), were associated with the global EDI-2 score, which measures EDI-related psychopathology (adjusted FDR-q=0.02 and 0.04, respectively). Moreover, rs81442 significantly modulated all the scales of the SCL-90R test that evaluates general psychopathology (FDR-q values ranged from 4.1E-04 to 0.011). A sliding-window analysis using adjacent 3-SNP haplotypes revealed a proximal region of the MSRA gene spanning 187.8 Kbp whose variability deeply affected psychopathological symptoms of the AN patients. Depression was the symptom that showed the strongest association with any of the constructed haplotypes (FDR-q=3.60E-06). No variants were found to be linked to AN risk or anthropometric parameters in patients or controls. Conclusions: Variability in the MSRA gene locus modulates psychopathology often presented by AN patients.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Variability in the antioxidant MSRA gene affects the psychopathology of patients with anorexia nervosa

González

García-Herráiz

Mota-Zamorano

et al. 2021

Acta Neuropsychiatr.

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“…54 Other multiphenotypic studies have identified BLK, XKR6, and MSRA as shared genes for depressive symptoms and neuroticism. 53 Clinically, selective serotonin reuptake inhibitors have been noted to decrease tinnitus distress for those patients with depression, 54 and our findings infer causality for MDD over tinnitus.…”

Section: Discussionmentioning

confidence: 52%

“…53 Analysis of cross-trait GWAS meta-analysis using a polygenic risk score for personality traits indicated that MSRA and XKR6 are within loci associated with neuroticism and response to selective serotonin reuptake inhibitor treatment. 53 MSRA demonstrates a high level of expression in brain tissue, and results indicate that certain loci have a combined effect on personality structure and outcome of antidepressant treatments in MDD. 54 Other multiphenotypic studies have identified BLK, XKR6, and MSRA as shared genes for depressive symptoms and neuroticism.…”

Section: Discussionmentioning

confidence: 99%

Novel Risk Loci in Tinnitus and Causal Inference With Neuropsychiatric Disorders Among Adults of European Ancestry

Clifford

Maihofer

Stein

et al. 2020

JAMA Otolaryngol Head Neck Surg

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IMPORTANCE Tinnitus affects at least 16 million US adults, but its pathophysiology is complicated, and treatment options remain limited. A heritable component has been identified in family and twin studies; however, no large-scale genome-wide association studies (GWAS) have been accomplished. OBJECTIVETo identify genetic risk loci associated with tinnitus, determine genetic correlations, and infer possible relationships of tinnitus with hearing loss and neuropsychiatric disorders and traits. DESIGN, SETTING, AND PARTICIPANTSA GWAS of self-reported tinnitus was performed in the UK Biobank (UKB) cohort using a linear mixed-model method implemented in BOLT-LMM (linear mixed model). Replication of significant findings was sought in the nonoverlapping US Million Veteran Program (MVP) cohort. A total of 172 995 UKB (discovery) and 260 832 MVP (replication) participants of European ancestry with self-report regarding tinnitus and hearing loss underwent genomic analysis. Linkage-disequilibrium score regression and mendelian randomization were performed between tinnitus and hearing loss and neuropsychiatric disorders. Data from the UKB were acquired and analyzed from September 24, 2018, to December 13, 2019. Data acquisition for the MVP cohort was completed July 22, 2019. Data analysis for both cohorts was completed on February 11, 2020. MAIN OUTCOMES AND MEASURESEstimates of single nucleotide variation (SNV)-based heritability for tinnitus, identification of genetic risk loci and genes, functional mapping, and replication were performed. Genetic association and inferred causality of tinnitus compared with hearing loss and neuropsychiatric disorders and traits were analyzed. RESULTSOf 172 995 UKB participants (53.7% female; mean [SD], 58.0 [8.2] years), 155 395 unrelated participants underwent SNV-based heritability analyses across a range of tinnitus phenotype definitions that explained approximately 6% of the heritability. The GWAS based on the most heritable model in the full UKB cohort identified 6 genome-wide significant loci and 27 genes in gene-based analyses, with replication of 3 of 6 loci and 8 of 27 genes in 260 832 MVP cohort participants (92.8% men; mean [SD] age, 63.8 [13.2] years). Mendelian randomization indicated that major depressive disorder had a permissive effect (β = 0.133; P = .003) and years of education had a protective effect (β = −0.322, P = <.001) on tinnitus, whereas tinnitus and hearing loss inferred a bidirectional association (β = 0.072, P = .001 and β = 1.546, P = <.001, respectively). CONCLUSIONS AND RELEVANCEThis large GWAS characterizes the genetic architecture of tinnitus, demonstrating modest but significant heritability and a polygenic profile with multiple significant risk loci and genes. Genetic correlation and inferred causation between tinnitus and major depressive disorder, educational level, and hearing impairment were identified, consistent with clinical and neuroimaging evidence. These findings may guide gene-based diagnostic and therapeutic approaches to this pervasive disor...

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Greenness, Genetic Predisposition, and Tinnitus

Yuan,

Li,

Tian

et al. 2024

Advanced Science

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This study aimed to investigate the association between residential greenness and tinnitus and the potential interaction between greenness and genetic predisposition to tinnitus. The normalized difference vegetation index (NDVI) is used to measure residential greenness. The tinnitus is defined based on self‐reported. In the cross‐sectional analyses, logistic regression models are used for the baseline sample of the United Kingdom Biobank cohort. In the secondary analysis, a Cox proportional hazard model is used for a subsample of participants who completed the tinnitus questionnaire at follow‐up. In the cross‐sectional analysis including 106471 participants, higher residential greenness is associated with lower odds of tinnitus for each interquartile range increase in continuous NDVI, with an adjusted odds ratio of 0.97 (95% confidence interval: 0.95 to 0.99) for tinnitus. A similar association is observed in the longitudinal analysis, with an adjusted hazard ratio of 0.92 (95% confidence interval: 0.86 to 0.98) for the association of NDVI increased per interquartile range with incident tinnitus. Moreover, there is a significant interaction between greenness and genetic predisposition to tinnitus (P < 0.05). This study suggested that residential greenness is negatively associated with tinnitus. Greenness and genetic predisposition to tinnitus are found to have a significant interaction.

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A genome-wide multiphenotypic association analysis identified common candidate genes for subjective well-being, depressive symptoms and neuroticism

Cited by 5 publications

References 49 publications

Variability in the antioxidant MSRA gene affects the psychopathology of patients with anorexia nervosa

Variability in the antioxidant MSRA gene affects the psychopathology of patients with anorexia nervosa

Novel Risk Loci in Tinnitus and Causal Inference With Neuropsychiatric Disorders Among Adults of European Ancestry

Greenness, Genetic Predisposition, and Tinnitus

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