Genome‐wide association studies of bipolar disorder: A systematic review of recent findings and their clinical implications

Ikeda, Masashi; Takeo, Satoshi; Kondo, Kenji; Iwata, Nakao

doi:10.1111/pcn.12611

Cited by 73 publications

(27 citation statements)

References 66 publications

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“…Genome‐wide association studies have shown that several genes, each of the modest effect, were identified as being associated with susceptibility for BD . However, these genetic effects are probabilistic and nonspecific for the identification of endophenotype .…”

Section: Circadian Rhythm Markers In Bdmentioning

confidence: 99%

Circadian rhythm in bipolar disorder: A review of the literature

Takaesu

2018

Psychiatry Clin Neurosci

156

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Sleep disturbances and circadian rhythm dysfunction have been widely demonstrated in patients with bipolar disorder (BD). Irregularity of the sleep-wake rhythm, eveningness chronotype, abnormality of melatonin secretion, vulnerability of clock genes, and the irregularity of social time cues have also been well-documented in BD. Circadian rhythm dysfunction is prominent in BD compared with that in major depressive disorders, implying that circadian rhythm dysfunction is a trait marker of BD. In the clinical course of BD, the circadian rhythm dysfunctions may act as predictors for the first onset of BD and the relapse of mood episodes. Treatments focusing on sleep disturbances and circadian rhythm dysfunction in combination with pharmacological, psychosocial, and chronobiological treatments are believed to be useful for relapse prevention. Further studies are therefore warranted to clarify the relation between circadian rhythm dysfunction and the pathophysiology of BD to develop treatment strategies for achieving recovery in BD patients.

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Section: Circadian Rhythm Markers In Bdmentioning

confidence: 99%

Circadian rhythm in bipolar disorder: A review of the literature

Takaesu

2018

Psychiatry Clin Neurosci

156

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“…Up to this point, the largest GWAS of schizophrenia and bipolar disorder comprise hundreds of thousands of individuals primarily of European descent (Stahl et al, 2019; Ripke et al, 2014; Zhiqiang et al, 2017). While studies of neuropsychiatric diseases in European and Asian ancestry populations continue to grow, the scarcity of studies in African American populations persists (Ikeda et al, 2017a).…”

Section: Introductionmentioning

confidence: 99%

Transcriptome association studies of neuropsychiatric traits in African Americans implicatePRMT7in schizophrenia

Fiorica

Wheeler

2019

Preprint

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14In the past fifteen years, genome-wide association studies (GWAS) have provided novel insight into the genetic architecture of various complex traits; however, this insight has been primarily focused on populations of European descent. This emphasis on European populations has led to individuals of recent African descent being grossly underrepresented in the study of genetics. With African Americans making up less than two percent of participants in neuropsychiatric GWAS, this discrepancy is magnified in diseases such as schizophrenia and bipolar disorder. In this study, we performed GWAS and the gene-based association method PrediXcan for schizophrenia (n=2,256) and bipolar disorder (n=1,019) in African American cohorts. In our PrediXcan analyses, we identified PRMT7 (P = 5.5 × 10 −6 , local false sign rate = 0.12) as significantly associated with schizophrenia following an adaptive shrinkage multiple testing adjustment. This association with schizophrenia was confirmed in the much larger, predominantly European, Psychiatric Genomics Consortium. In addition to the PRMT7 association with schizophrenia, we identified rs10168049 (P = 1.0 × 10 −6 ) as a potential candidate locus for bipolar disorder with highly divergent allele frequencies across populations, highlighting the need for diversity in genetic studies.

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“…Subsequently, functional magnetic resonance imaging studies have succeeded in connecting phenomena of the mind to that in the brain, which has led to the promising new treatment strategy of neurofeedback . Recent genome‐wide association studies have shown the utility of polygenic risk scores (PRS), and analyses using PRS have confirmed traditional clinical findings, for example, early age at onset in major depression as a risk factor of bipolar disorder . Moreover, development of induced pluripotent cell technology has enabled the analysis of patients’ neurons in vitro for the first time …”

mentioning

confidence: 99%

“…However, such remarkable progress has not yet caused innovation in clinical practice in psychiatry, and daily practice in clinics is mostly similar to that of several decades ago. Paradoxically, the progress of biological research has obscured the boundary of diagnostic categories: The same classes of drugs are effective for different types of diseases and there is an overlap in genetic, neuroimaging, and cellular findings across different mental disorders . This may indicate that current biological studies in psychiatry have not grown out of understanding mental disorders’ symptomatic‐level phenomena.…”

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confidence: 99%