Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia

Nakahara, Soichiro; Medland, Sarah E.; Turner, Jessica A.; Calhoun, Vince D.; Lim, Kelvin O.; Mueller, Bryon A.; Bustillo, Juan; O'Leary, Daniel S.; Vaidya, Jatin G.; McEwen, Sarah; Voyvodic, James T.; Belger, Ayşenil; Mathalon, Daniel H.; Ford, Judith M.; Guffanti, Guia; Macciardi, Fabìo; Potkin, Steven G.; Erp, Theo G.M. van

doi:10.1016/j.schres.2018.05.041

Cited by 28 publications

(37 citation statements)

References 42 publications

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“…Since attention is strongly impaired in individuals with SZ, most studies considered this domain in their analyses. Significant associations between SZ-PRS and attention are only reported by Nakahara et al [27] , while other studies did not reveal any significant association between SZ-PRS and attention [28,33] . Post hoc analysis by Xavier et al [35] revealed a significant association between SZ-PRS and vigilance but the finding did not survive correction for multiple testing.…”

Section: Attention/vigilancementioning

confidence: 86%

“…While the studies of Ranlund and Whalley [28,34] were not able to find any association between SZ-PRS and verbal learning, Nakahara et al [27] showed a significant association between verbal learning and SZ-PRS. Also, in this case the post hoc analysis by Xavier et al [35] on a possible association between SZ-PRS and memory did not survive correction for multiple testing.…”

Section: Verbal Learning and Memorymentioning

confidence: 88%

“…They report a significant association between the outcome measures perseverative responses, perseverative errors, conceptual level response and failure to maintain set and SZ-PRS, even though the overall outcome measure for the WCST did not reveal any significant association with SZ-PRS [33] . For problem solving Nakahara et al [27] report a significant negative correlation with SZ-PRS. Post hoc analysis by Xavier et al [35] did not reveal a significant association between SZ-PRS and reasoning.…”

Section: Reasoning and Problem Solvingmentioning

confidence: 99%

“…Nakahara et al, 2018 [27] • C: N = 136 Ranlund et al, 2017 [28] • Shafee et al, 2018 [29] Bipolar-Schizophrenia Network for Intermediate Phenotypes: van Os et al, 2017 [30] Genetic Risk and Outcome of Psychosis: • IQ (information, block design, digit symbol coding, arithmetic (WAIS); baseline & 3-year follow-up) • IQ (information (every third item), block design (uneven items), digit symbol coding, arithmetic (uneven items) (WAIS-III short form); 6-year follow-up)…”

Section: Author and Year Sample Domain (Test) *Significantmentioning

confidence: 99%

“…Only the study of Nakaraha et al [27] considered visual learning and was able to show a significant association with SZ-PRS.…”

Section: Visual Learning and Memorymentioning

confidence: 99%

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Let’s Talk about the Association between Schizophrenia Polygenic Risk Scores and Cognition in Patients and the General Population: A Review

2018

J Psychiatry Brain Sci

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In the late 19th century, Emil Kraepelin divided endogenous psychosis into manic-depressive psychosis and dementia praecox. The latter term described individuals with schizophrenia and highlights cognitive deficits as a core feature of this illness. Since first degree relatives show lower cognitive performance than healthy controls, but better performance than patients, cognitive functions are discussed as potential endophenotypes for schizophrenia. During the last years, several studies have explored the relationship between schizophrenia polygenic risk scores and cognition both in individuals with psychiatric diseases and the general population. Current research shows mixed results for specific cognitive domains as well as general cognitive abilities and intelligence. These ambiguous results in parts might be due to the heterogeneity of neuropsychological tests used to measure various cognitive domains. Most studies are also underpowered, given the small to moderate effects of schizophrenia polygenic risk scores on cognition. As sufficient sample sizes become more and more available by international consortia and national registries, future studies will probably shed light on the biological relationship between schizophrenia and cognition.

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Section: Attention/vigilancementioning

confidence: 86%

Section: Verbal Learning and Memorymentioning

confidence: 88%

Section: Reasoning and Problem Solvingmentioning

confidence: 99%

Section: Author and Year Sample Domain (Test) *Significantmentioning

confidence: 99%

“…Only the study of Nakaraha et al [27] considered visual learning and was able to show a significant association with SZ-PRS.…”

Section: Visual Learning and Memorymentioning

confidence: 99%

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Let’s Talk about the Association between Schizophrenia Polygenic Risk Scores and Cognition in Patients and the General Population: A Review

2018

J Psychiatry Brain Sci

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Meta‐analysis of age‐related cognitive decline reveals a novel locus for the attention domain and implicates a COVID‐19‐related gene for global cognitive function

Acharya

Fan

Snitz

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONCognitive abilities have substantial heritability throughout life, as shown by twin‐ and population‐based studies. However, there is limited understanding of the genetic factors related to cognitive decline in aging across neurocognitive domains.METHODSWe conducted a meta‐analysis on 3045 individuals aged ≥65, derived from three population‐based cohorts, to identify genetic variants associated with the decline of five neurocognitive domains (attention, memory, executive function, language, visuospatial function) and global cognitive decline. We also conducted gene‐based and functional bioinformatics analyses.RESULTSApolipoprotein E (APOE)4 was significantly associated with decline of memory (p = 5.58E‐09) and global cognitive function (p = 1.84E‐08). We identified a novel association with attention decline on chromosome 9, rs6559700 (p = 2.69E‐08), near RASEF. Gene‐based analysis also identified a novel gene, TMPRSS11D, involved in the activation of SARS‐CoV‐2, to be associated with the decline in global cognitive function (p = 4.28E‐07).DISCUSSIONDomain‐specific genetic studies can aid in the identification of novel genes and pathways associated with decline across neurocognitive domains.Highlights rs6559700 was associated with decline of attention. APOE4 was associated with decline of memory and global cognitive decline. TMPRSS11D, a gene involved in the activation of SARS‐CoV‐2, was implicated in global cognitive decline. Cognitive domain abilities had both unique and shared molecular pathways across the domains.

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Structural changes in the hippocampus as a biomarker for cognitive improvements in neuropsychiatric disorders: A systematic review

Ott

Johnson

Macoveanu

2019

European Neuropsychopharmacology

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Polygenic risk score, genome-wide association, and gene set analyses of cognitive domain deficits in schizophrenia

Cited by 28 publications

References 42 publications

Let’s Talk about the Association between Schizophrenia Polygenic Risk Scores and Cognition in Patients and the General Population: A Review

Let’s Talk about the Association between Schizophrenia Polygenic Risk Scores and Cognition in Patients and the General Population: A Review

Meta‐analysis of age‐related cognitive decline reveals a novel locus for the attention domain and implicates a COVID‐19‐related gene for global cognitive function

Structural changes in the hippocampus as a biomarker for cognitive improvements in neuropsychiatric disorders: A systematic review

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