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A Population-Based Study of Shared Genetic Variation Between Premorbid IQ and Psychosis Among Male Twin Pairs and Sibling Pairs From Sweden

Published on May 1, 2012in Archives of General Psychiatry
· DOI :10.1001/archgenpsychiatry.2011.1370
Timothy M Fowler4
Estimated H-index: 4
(University of Birmingham),
Stanley Zammit47
Estimated H-index: 47
(UoB: University of Bristol)
+ 1 AuthorsFinn Rasmussen57
Estimated H-index: 57
Cite
Abstract
Context: The strong association between lower IQ and risk for psychosis has led to the suggestion that the search for genes influencing cognition may provide a useful strategy for examining the genetic origins of psychosis. However, research in this area has generally used designs in which twin pairs are selected by case status and with assessment of IQ after the onset of psychosis rather than longitudinal population-based samples. Objective: To examine the relationship and shared genetic origin between premorbid IQ and psychotic disorders in a longitudinal population-based cohort. Design: Genetically informative longitudinal study. Setting: Population-based cohort in Sweden. Participants Individuals were identified from the population-based Swedish Multi-Generation Register and consisted of male sibling (n = 369 960), monozygotic twin (n = 1986), and dizygotic twin (n = 2253) pairs born between January 1951 and December 1976. Their IQs were measured during compulsory military conscription. Main Outcome Measure: Individuals having a subsequent diagnosis of psychosis were identified via the Swedish National Hospital Discharge Register. Results: Heritability estimates for IQ and psychosis were similar to previous estimates, approximately 69% and 56%, respectively. However, the phenotypic correlation between IQ and psychosis was only −0.11, of which 91% was due to shared genetic influences. The proportion of genetic variance for psychosis shared with that for IQ was approximately 7%. Conclusions: Using IQ as a phenotype to identify genes that have an important role in the genetic origin of schizophrenia is unlikely to be a successful strategy. The low correlation seen in this study between premorbid IQ and psychosis vs the higher correlations reported in the literature with postmorbid IQ suggests the correlation between these phenotypes has more to do with the influence that the onset of psychosis has on cognitive functioning than with shared genetic origin.
  • References (32)
  • Citations (43)
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References32
Newest
Published on Jul 1, 2011in Schizophrenia Bulletin7.29
Verity C. Leeson15
Estimated H-index: 15
(Imperial College London),
Pranev Sharma3
Estimated H-index: 3
(Imperial College London)
+ 3 AuthorsEileen M. Joyce47
Estimated H-index: 47
(UCL Institute of Neurology)
Comparison of current and estimated premorbid IQ in schizophrenia suggests that there are subgroups with low IQ, deteriorated IQ (DIQ), or preserved IQ and that this is established by psychosis onset. There are no controlled studies examining the trajectory of these IQ subgroups longitudinally or their relationship with clinical and social outcomes. Of 129 individuals with first-episode schizophrenia or schizoaffective disorder, 25% showed stable low IQ, 31% showed stable IQ in the average/high ...
Published on Sep 1, 2010in Archives of General Psychiatry
Timothea Toulopoulou37
Estimated H-index: 37
,
Terry E. Goldberg39
Estimated H-index: 39
+ 10 AuthorsMing T. Tsuang120
Estimated H-index: 120
(UCSD: University of California, San Diego)
Content The DSM-IV concept of schizophrenia offers diagnostic reliability but etiologic and pathologic heterogeneity, which probably contributes to the inconsistencies in genetic studies. One solution is to identify intermediate phenotypes, “narrower” constructs of liability, that hypothetically share genetic risk with the disorder. Although a variety of candidate intermediate phenotypes have emerged, few have explicitly quantified the extent of their genetic overlap with schizophrenia. Objectiv...
Published on Jul 1, 2010in Archives of General Psychiatry
M. Owen141
Estimated H-index: 141
,
Nicholas John Craddock99
Estimated H-index: 99
,
Michael C. O’Donovan120
Estimated H-index: 120
This article reviews recent genome-wide association studies (GWAS) of schizophrenia and considers future research directions. Until recently, genome-wide scans for disease risk variants were based on linkage analysis, an approach that can detect only those alleles that confer relatively large effects. The main alternative was the candidate gene association study, which, although better powered than linkage for weak genetic effects, is problematic for phenotypes where pathogenesis is largely unkn...
Published on Feb 1, 2010in British Journal of Psychiatry7.23
James H. MacCabe29
Estimated H-index: 29
,
Mats Lambe51
Estimated H-index: 51
(KI: Karolinska Institutet)
+ 5 AuthorsChristina M. Hultman65
Estimated H-index: 65
(KI: Karolinska Institutet)
Background Anecdotal and biographical reports suggest that bipolar disorder may be associated with high IQ or creativity, but evidence for any such connection is weak. Aims To investigate possible associations between scholastic achievement and later bipolar disorder, using prospective data, in a whole-population cohort study. Method Using individual school grades from all individuals finishing compulsory schooling in Sweden between 1988 and 1997, we tested associations between scholastic achiev...
Published on Jul 1, 2009in Human Genetics5.21
Ian J. Deary121
Estimated H-index: 121
(Edin.: University of Edinburgh),
Willene Johnson1
Estimated H-index: 1
(Edin.: University of Edinburgh),
Lorna M. Houlihan11
Estimated H-index: 11
(Edin.: University of Edinburgh)
Individual differences in intelligence (cognitive abilities) are a prominent aspect of human psychology, and play a substantial role in influencing important life outcomes. Their phenotypic structure—as described by the science of psychometrics—is well understood and well replicated. Approximately half of the variance in a broad range of cognitive abilities is accounted by a general cognitive factor (g), small proportions of cognitive variance are caused by separable broad domains of mental func...
Published on Jul 1, 2009in Human Genetics5.21
Michael C. O’Donovan120
Estimated H-index: 120
(Cardiff University),
Nicholas John Craddock99
Estimated H-index: 99
(Cardiff University),
M. Owen141
Estimated H-index: 141
(Cardiff University)
The major psychotic illnesses, schizophrenia and bipolar disorder (BD), are among the most heritable common disorders, but finding specific susceptibility genes for them has not been straightforward. The reasons are widely assumed to include lack of valid phenotypic definition, absence of good theories of pathophysiology for candidate gene studies, and the involvement of many genes, each making small contributions to population risk. Within the last year or so, a number of genome wide associatio...
Published on May 1, 2008in American Journal of Psychiatry13.65
Kristen A. Woodberry15
Estimated H-index: 15
,
Anthony J. Giuliano18
Estimated H-index: 18
,
Larry J. Seidman104
Estimated H-index: 104
Objective: Over the past three decades, there have been significant changes in the diagnostic criteria for schizophrenia as well as changes in measurement of IQ. The last quantitative review of the literature on premorbid IQ in schizophrenia was published more than two decades ago. Since that time, there have been many published studies of data sets pertaining to this issue. The purpose of the present review was to provide an updated meta-analysis of premorbid IQ in individuals who later develop...
Published on May 1, 2008in Genetic Epidemiology2.50
Karri Silventoinen50
Estimated H-index: 50
(UH: University of Helsinki),
Pke Magnusson80
Estimated H-index: 80
(KI: Karolinska Institutet)
+ 2 AuthorsFinn Rasmussen57
Estimated H-index: 57
(KI: Karolinska Institutet)
Moderate heritability for skeletal muscle strength has been reported in twin studies, but genetic co-variation between muscle strength at different parts of body and body size is not well known. Further, representativeness of twin cohorts needs to be critically evaluated. Height, weight, elbow flexion, hand grip and knee extension strength were measured in young adulthood in 1,139,963 Swedish men born between 1951 and 1976. We identified 154,970 full-brother pairs and 1582 monozygotic (MZ) and 1...
Published on Apr 1, 2008in Archives of General Psychiatry
Timothea Toulopoulou37
Estimated H-index: 37
(Harvard University),
Marco Picchioni34
Estimated H-index: 34
('KCL': King's College London)
+ 4 AuthorsRobin M. Murrayand143
Estimated H-index: 143
('KCL': King's College London)
Context The use of endophenotypes, biological traits that increase the liability to a disorder, represents one strategy to facilitate the detection of susceptibility genes for complex behavioral disorders such as schizophrenia. Establishing that a candidate trait is both heritable and linked genetically to schizophrenia is integral to its validity as an endophenotypic marker. Neurocognitive deficits are among the most promising indicators of increased risk for schizophrenia; however, it is not c...
Published on Oct 1, 2007in Molecular Psychiatry11.97
James Walters33
Estimated H-index: 33
,
M. Owen141
Estimated H-index: 141
Cited By43
Newest
Published on Feb 1, 2019in Brain11.81
Timothea Toulopoulou37
Estimated H-index: 37
,
Xw Zhang2
Estimated H-index: 2
(HKU: University of Hong Kong)
+ 5 AuthorsDaniel R. Weinberger (Johns Hopkins University)
Published on Jan 4, 2019in Molecular Psychiatry11.97
Olav B. Smeland13
Estimated H-index: 13
(Oslo University Hospital),
Shahram Bahrami3
Estimated H-index: 3
(Oslo University Hospital)
+ 12 AuthorsNils Eiel Steen16
Estimated H-index: 16
(Oslo University Hospital)
Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders associated with cognitive impairment, which is considered a major determinant of functional outcome. Despite this, the etiology of the cognitive impairment is poorly understood, and no satisfactory cognitive treatments exist. Increasing evidence indicates that genetic risk for SCZ may contribute to cognitive impairment, whereas the genetic relationship between BD and cognitive function remains unclear. Here, we combined la...
Published on Dec 1, 2018in Translational Psychiatry5.18
Rebecca Shafee9
Estimated H-index: 9
(Broad Institute),
Pranav Nanda6
Estimated H-index: 6
(Columbia University)
+ 16 AuthorsScot K. Hill4
Estimated H-index: 4
(RFUMS: Rosalind Franklin University of Medicine and Science)
Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of polygenetic risk for schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BAC...
Published on Nov 1, 2018in Biological Psychiatry11.50
Holger J. Sørensen19
Estimated H-index: 19
(Lundbeck),
Holger J. Sørensen7
Estimated H-index: 7
(Lundbeck)
+ 8 AuthorsOle Mors59
Estimated H-index: 59
(Lundbeck)
Background: Studies have suggested that poor school achievement is associated with increased risk of schizophrenia; however, the possible genetic contribution to this association is unknown. We investigated the possible effect of the polygenic risk score (PRS) for schizophrenia (PRS) and for educational attainment (PRS) on the association between school performance and later schizophrenia. Methods: We conducted a case-cohort study on a Danish population-based sample born from 1987 to 1995 compri...
Published on Feb 1, 2018in Scandinavian Journal of Psychology1.38
Olav B. Smeland13
Estimated H-index: 13
(Oslo University Hospital),
Ole A. Andreassen75
Estimated H-index: 75
(Oslo University Hospital)
Published on Feb 1, 2018in Psychological Medicine5.64
Josephine Mollon6
Estimated H-index: 6
,
Avi Reichenberg52
Estimated H-index: 52
Published on Oct 1, 2017in JAMA Psychiatry15.92
Olav B. Smeland13
Estimated H-index: 13
(UCSD: University of California, San Diego),
Oleksandr Frei7
Estimated H-index: 7
(University of Oslo)
+ 19 AuthorsAree Witoelar13
Estimated H-index: 13
(University of Oslo)
Importance Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia m...
Published on Sep 1, 2017in Schizophrenia Research: Cognition
Aja Neergaard Greve5
Estimated H-index: 5
(Lundbeck),
Ole Mors59
Estimated H-index: 59
(Lundbeck)
+ 3 AuthorsLiselotte Petersen24
Estimated H-index: 24
(Lundbeck)
Results from twin, family, and adoption studies all suggest that general intelligence is highly heritable. Several studies have shown lower premorbid intelligence in individuals before the onset of both mood disorders and psychosis, as well as in children and adolescents at genetic high risk for developing schizophrenia. Based on these findings, we aim to investigate if the association between educational achievement in parents and intelligence in their offspring is influenced by schizophrenia o...
Published on Jul 1, 2017in Schizophrenia Bulletin7.29
Gabriëlla A.M. Blokland10
Estimated H-index: 10
(Broad Institute),
Raquelle I. Mesholam-Gately23
Estimated H-index: 23
(Harvard University)
+ 7 AuthorsTracey L. Petryshen23
Estimated H-index: 23
(Broad Institute)
Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The prop...
Published on May 1, 2017in Schizophrenia Research4.57
W. C. Hochberger2
Estimated H-index: 2
(RFUMS: Rosalind Franklin University of Medicine and Science),
T. Combs1
Estimated H-index: 1
(RFUMS: Rosalind Franklin University of Medicine and Science)
+ 8 AuthorsScot K. Hill4
Estimated H-index: 4
(RFUMS: Rosalind Franklin University of Medicine and Science)
Abstract Patients with schizophrenia show a deficit in cognitive ability compared to estimated premorbid and familial intellectual abilities. However, the degree to which this pattern holds across psychotic disorders and is familial is unclear. The present study examined deviation from expected cognitive level in schizophrenia, schizoaffective disorder, and psychotic bipolar disorder probands and their first-degree relatives. Using a norm-based regression approach, parental education and WRAT-IV...
View next paperMolecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: a report from the Cognitive Genomics consorTium (COGENT).