Cognitive performances across individuals at high genetic risk for schizophrenia, high genetic risk for bipolar disorder, and low genetic risks: a combined polygenic risk score approach

Ohi, Kazutaka; Nishizawa, Daisuke; Sugiyama, Shunsuke; Takai, Kentaro; Fujikane, Daisuke; Kuramitsu, Ayumi; Hasegawa, Junko; Soda, Midori; Kitaichi, Kiyoyuki; Hashimoto, Ryota; Ikeda, Kazutaka; Shioiri, Toshiki

doi:10.1017/s0033291722001271

Cited by 14 publications

(27 citation statements)

References 58 publications

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“…The complete lack of correlation (Figure 4, Table S3) suggests that the cognitive deficits we observed among affected participants do not reflect overlapping genetic determinants between mood disorders and cognition. This finding is supported by the polygenic risk score (PRS) literature, which shows no correlation between bipolar disorder PRS and cognitive functioning (Ranlund et al 2018, Ohi et al 2022).…”

Section: Discussionsupporting

confidence: 61%

Independent Inheritance of Cognition and Bipolar Disorder in a Family Sample

D’Amico,

Sung,

Arbona-Lampaya

et al. 2023

Preprint

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Background The basis of cognitive deficits in people with bipolar disorder (BD) has not been elucidated. These deficits may be the result of the illness or its treatment, but could also reflect genetic risk factors that are shared between BD and cognition. We investigated this question using empirical genetic relationships within a sample of patients with BD and their unaffected relatives. Methods Participants with bipolar I, II, or schizoaffective disorder (narrow BD, n=69), related mood disorders (broad BD, n=135), and their clinically unaffected relatives (n=227) completed tests of matrix reasoning, trail making, digit-symbol coding, semantic short-term recall, and affect recognition (DANVA2). General cognitive function (g) was quantified via principal components analysis (PCA). Heritability and genetic correlations were estimated with SOLAR-Eclipse. Results Participants with a narrow or broad BD diagnosis showed deficits in g, though affect recognition was not impaired. Cognitive performance was significantly heritable (h2 = 0.322 for g, p<0.005). Coheritability between BD and cognition was small (coheritability for g & Narrow = 0.0184, for g & Broad = 0.0327) and healthy relatives of those with BD were cognitively unimpaired. Conclusions In this family sample, cognitive deficits were present in participants with BD, but social cognition, measured by affect recognition, was not impaired. Deficits were largely not explained by overlapping genetic determinants of mood and cognition. These findings support the view that cognition comprises separable social and non-social domains and that cognitive deficits in BD are largely the result of the illness or its treatment.

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Section: Discussionsupporting

confidence: 61%

Independent Inheritance of Cognition and Bipolar Disorder in a Family Sample

D’Amico,

Sung,

Arbona-Lampaya

et al. 2023

Preprint

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“…The subjects for this study were 172 patients with SCZ (71 males/101 females, mean age ± SD: 44.8 ± 13.8 years), 75 unaffected FRs (14 siblings/54 parents/7 children, 25 males/50 females, age: 59.5 ± 14.5 years) and 158 HCs (106 males/52 females, age: 36.4 ± 14.4 years). The study sample was recruited from the Schizophrenia Non-Affected Relative Project (SNARP) at Kanazawa Medical University (Kataoka et al, 2020;Ohi et al, 2019aOhi et al, , 2020aOhi et al, , 2020bOhi et al, , 2021aOhi et al, , 2022b. All subjects were of Japanese descent.…”

Section: Subjectsmentioning

confidence: 99%

Olfactory identification ability among schizophrenia patients, their first-degree relatives and healthy subjects

Fukuda

Ohi

Fujikane

et al. 2023

Aust N Z J Psychiatry

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Objective: Olfactory impairments, including identification, have been reported in patients with schizophrenia, while few studies have examined the olfactory function of unaffected first-degree relatives of patients with schizophrenia, and the sample sizes of first-degree relatives were relatively small. Here, we investigated olfactory identification ability among patients with schizophrenia, first-degree relatives and healthy controls (HCs) using relatively large sample sizes at a single institute. Methods: To assess olfactory identification ability, the open essence odorant identification test was administered to 172 schizophrenia patients, 75 first-degree relatives and 158 healthy controls. Differences in olfactory identification and correlations between olfactory ability and clinical variables were examined among these participants. Results: We found a significant difference in olfactory identification ability among the diagnostic groups ( p = 7.65 × 10−16). Schizophrenia patients displayed lower olfactory identification ability than first-degree relatives (Cohen’s d = −0.57, p = 3.13 × 10−6) and healthy controls ( d = −1.00, p = 2.19 × 10−16). Furthermore, first-degree relatives had lower olfactory identification ability than healthy controls ( d = −0.29, p = 0.039). Olfactory identification ability moderately and negatively correlated with the duration of illness ( r = −0.41, p = 1.88 × 10−8) and negative symptoms ( r = −0.28, p = 1.99 × 10−4) in schizophrenia patients, although the correlation with the duration of illness was affected by aging ( r = −0.24). Conclusions: Our results demonstrated that schizophrenia patients have impaired olfactory identification ability compared with first-degree relatives and healthy controls, and the impaired olfactory identification ability of first-degree relatives was intermediate between those in schizophrenia patients and healthy controls. Olfactory identification ability was relatively independent of clinical variables. Therefore, olfactory identification ability might be an intermediate phenotype for schizophrenia.

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Section: Introductionmentioning

confidence: 96%

“…On the other hand, the PRSs between the case‒control groups highly overlapped 12 14 15. Therefore, we divided participants into decile category groups based on PRSs and found that individuals in higher deciles for SZ PRSs had up to approximately fourfold, sixfold and twofold higher risk of SZ and PRSs for BD and SZ versus BD than those in lower deciles for SZ PRSs, respectively 14. In addition, we investigated differences in cognitive impairments that were a core feature of SZ and BD and that were more prominent in SZ patients than in BD patients16 17 among three genetic risk groups: the genetic SZ risk, genetic BD risk and low genetic risks for SZ and BD groups, stratified by combinations of the PRSs for SZ, BD and SZ versus BD 14.…”

Section: Introductionmentioning

confidence: 99%

“…We indicated that the PRSs for SZ, BD and SZ versus BD based on the GWASs from the PGC were higher in SZ patients than in healthy controls (HCs) 14. On the other hand, the PRSs between the case‒control groups highly overlapped 12 14 15. Therefore, we divided participants into decile category groups based on PRSs and found that individuals in higher deciles for SZ PRSs had up to approximately fourfold, sixfold and twofold higher risk of SZ and PRSs for BD and SZ versus BD than those in lower deciles for SZ PRSs, respectively 14.…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder

Ohi,

Shimada,

Soda

et al. 2024

BMJ Ment Health

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BackgroundGenetic and environmental factors contribute to the pathogenesis of schizophrenia (SZ) and bipolar disorder (BD). Among genetic risk groups stratified by combinations of Polygenic Risk Score (PRS) deciles for SZ, BD and SZ versus BD, genetic SZ risk groups had high SZ risk and prominent cognitive impairments. Furthermore, epigenetic alterations are implicated in these disorders. However, it was unclear whether DNA Methylation Risk Scores (MRSs) for SZ risk derived from blood and brain tissues were associated with SZ risk, particularly the PRS-stratified genetic SZ risk group.MethodsEpigenome-wide association studies (EWASs) of SZ risk in whole blood were preliminarily conducted between 66 SZ patients and 30 healthy controls (HCs) and among genetic risk groups (individuals with low genetic risk for SZ and BD in HCs (n=30) and in SZ patients (n=11), genetic BD risk in SZ patients (n=25) and genetic SZ risk in SZ patients (n=30)) stratified by combinations of PRSs for SZ, BD and SZ versus BD. Next, differences in MRSs based on independent EWASs of SZ risk in whole blood, postmortem frontal cortex (FC) and superior temporal gyrus (STG) were investigated among our case‒control and PRS-stratified genetic risk status groups.ResultsAmong case‒control and genetic risk status groups, 33 and 351 genome-wide significant differentially methylated positions (DMPs) associated with SZ were identified, respectively, many of which were hypermethylated. Compared with the low genetic risk in HCs group, the genetic SZ risk in SZ group had 39 genome-wide significant DMPs, while the genetic BD risk in SZ group had only six genome-wide significant DMPs. The MRSs for SZ risk derived from whole blood, FC and STG were higher in our SZ patients than in HCs in whole blood and were particularly higher in the genetic SZ risk in SZ group than in the low genetic risk in HCs and genetic BD risk in SZ groups. Conversely, the MRSs for SZ risk based on our whole-blood EWASs among genetic risk groups were also associated with SZ in the FC and STG. There were no correlations between the MRSs and PRSs.ConclusionsThese findings suggest that the MRS is a potential genetic marker in understanding SZ, particularly in patients with a genetic SZ risk.

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Cognitive performances across individuals at high genetic risk for schizophrenia, high genetic risk for bipolar disorder, and low genetic risks: a combined polygenic risk score approach

Cited by 14 publications

References 58 publications

Independent Inheritance of Cognition and Bipolar Disorder in a Family Sample

Independent Inheritance of Cognition and Bipolar Disorder in a Family Sample

Olfactory identification ability among schizophrenia patients, their first-degree relatives and healthy subjects

Genome-wide DNA methylation risk scores for schizophrenia derived from blood and brain tissues further explain the genetic risk in patients stratified by polygenic risk scores for schizophrenia and bipolar disorder

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