Polygenic Risk for Schizophrenia Is Associated with Cognitive Change Between Childhood and Old Age

Andrew M McIntosh; Alan Gow; Michelle Luciano; Gail Davies; David C Liewald; Sarah E Harris; Janie Corley; Jeremy Hall; John M Starr; David J Porteous; Albert Tenesa; Peter M Visscher; Ian J Deary

doi:10.1016/j.biopsych.2013.01.011

Polygenic Risk for Schizophrenia Is Associated with Cognitive Change Between Childhood and Old Age

Andrew M McIntosh, Alan Gow, Michelle Luciano, Gail Davies, David C Liewald, Sarah E Harris, Janie Corley, Jeremy Hall, John M Starr, David J Porteous, Albert Tenesa, Peter M Visscher, Ian J Deary

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Genome-wide association studies (GWAS) have shown a polygenic component to the risk of schizophrenia. The disorder is associated with impairments in general cognitive ability that also have a substantial genetic contribution. No study has determined whether cognitive impairments can be attributed to schizophrenia's polygenic architecture using data from GWAS. METHODS: Members of the Lothian Birth Cohort 1936 (LBC1936, n = 937) were assessed using the Moray House Test at age 11 and with the Moray House Test and a further cognitive battery at age 70. To create polygenic risk scores for schizophrenia, we obtained data from the latest GWAS of the Psychiatric GWAS Consortium on Schizophrenia. Schizophrenia polygenic risk profile scores were calculated using information from the Psychiatric GWAS Consortium on Schizophrenia GWAS. RESULTS: In LBC1936, polygenic risk for schizophrenia was negatively associated with IQ at age 70 but not at age 11. Greater polygenic risk for schizophrenia was associated with more relative decline in IQ between these ages. These findings were maintained when the results of LBC1936 were combined with that of the independent Lothian Birth Cohort 1921 (n = 517) in a meta-analysis. CONCLUSIONS: Increased polygenic risk of schizophrenia is associated with lower cognitive ability at age 70 and greater relative decline in general cognitive ability between the ages of 11 and 70. Common genetic variants may underlie both cognitive aging and risk of schizophrenia.

Original language	English
Pages (from-to)	938-943
Journal	Biological Psychiatry
Volume	73
Issue number	10
Early online date	16 Feb 2013
DOIs	https://doi.org/10.1016/j.biopsych.2013.01.011
Publication status	Published - 2013

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10.1016/j.biopsych.2013.01.011

McIntosh AM Polygenic risk of schizophrenia Biol Psych 2012Final published version, 100 KB

Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.
Maclullich, A. (Principal Investigator)
1/09/13 → 31/08/19
Project: Research
RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.
Deary, I. (Principal Investigator), Gale, C. (Co-investigator), Holmes, M. (Co-investigator), Logie, P. (Co-investigator), Maclullich, A. (Co-investigator), Porteous, D. (Co-investigator), Seckl, J. (Co-investigator), Starr, J. (Co-investigator), Wardlaw, J. (Co-investigator) & Okely, J. (Researcher)
1/09/13 → 31/08/19
Project: Research
A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921
Deary, I. (Principal Investigator), Bates, T. (Co-investigator), Gow, A. (Co-investigator) & Starr, J. (Co-investigator)
UK central government bodies/local authorities, health and hospital authorities
1/01/11 → 31/12/12
Project: Research

Cite this

McIntosh, A. M., Gow, A., Luciano, M., Davies, G., Liewald, D. C., Harris, S. E., Corley, J., Hall, J., Starr, J. M., Porteous, D. J., Tenesa, A., Visscher, P. M., & Deary, I. J. (2013). Polygenic Risk for Schizophrenia Is Associated with Cognitive Change Between Childhood and Old Age. Biological Psychiatry, 73(10), 938-943. https://doi.org/10.1016/j.biopsych.2013.01.011

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title = "Polygenic Risk for Schizophrenia Is Associated with Cognitive Change Between Childhood and Old Age",

abstract = "BACKGROUND: Genome-wide association studies (GWAS) have shown a polygenic component to the risk of schizophrenia. The disorder is associated with impairments in general cognitive ability that also have a substantial genetic contribution. No study has determined whether cognitive impairments can be attributed to schizophrenia's polygenic architecture using data from GWAS. METHODS: Members of the Lothian Birth Cohort 1936 (LBC1936, n = 937) were assessed using the Moray House Test at age 11 and with the Moray House Test and a further cognitive battery at age 70. To create polygenic risk scores for schizophrenia, we obtained data from the latest GWAS of the Psychiatric GWAS Consortium on Schizophrenia. Schizophrenia polygenic risk profile scores were calculated using information from the Psychiatric GWAS Consortium on Schizophrenia GWAS. RESULTS: In LBC1936, polygenic risk for schizophrenia was negatively associated with IQ at age 70 but not at age 11. Greater polygenic risk for schizophrenia was associated with more relative decline in IQ between these ages. These findings were maintained when the results of LBC1936 were combined with that of the independent Lothian Birth Cohort 1921 (n = 517) in a meta-analysis. CONCLUSIONS: Increased polygenic risk of schizophrenia is associated with lower cognitive ability at age 70 and greater relative decline in general cognitive ability between the ages of 11 and 70. Common genetic variants may underlie both cognitive aging and risk of schizophrenia.",

author = "McIntosh, {Andrew M} and Alan Gow and Michelle Luciano and Gail Davies and Liewald, {David C} and Harris, {Sarah E} and Janie Corley and Jeremy Hall and Starr, {John M} and Porteous, {David J} and Albert Tenesa and Visscher, {Peter M} and Deary, {Ian J}",

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doi = "10.1016/j.biopsych.2013.01.011",

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AU - McIntosh, Andrew M

AU - Gow, Alan

AU - Luciano, Michelle

AU - Davies, Gail

AU - Liewald, David C

AU - Harris, Sarah E

AU - Corley, Janie

AU - Hall, Jeremy

AU - Starr, John M

AU - Porteous, David J

AU - Tenesa, Albert

AU - Visscher, Peter M

AU - Deary, Ian J

PY - 2013

Y1 - 2013

N2 - BACKGROUND: Genome-wide association studies (GWAS) have shown a polygenic component to the risk of schizophrenia. The disorder is associated with impairments in general cognitive ability that also have a substantial genetic contribution. No study has determined whether cognitive impairments can be attributed to schizophrenia's polygenic architecture using data from GWAS. METHODS: Members of the Lothian Birth Cohort 1936 (LBC1936, n = 937) were assessed using the Moray House Test at age 11 and with the Moray House Test and a further cognitive battery at age 70. To create polygenic risk scores for schizophrenia, we obtained data from the latest GWAS of the Psychiatric GWAS Consortium on Schizophrenia. Schizophrenia polygenic risk profile scores were calculated using information from the Psychiatric GWAS Consortium on Schizophrenia GWAS. RESULTS: In LBC1936, polygenic risk for schizophrenia was negatively associated with IQ at age 70 but not at age 11. Greater polygenic risk for schizophrenia was associated with more relative decline in IQ between these ages. These findings were maintained when the results of LBC1936 were combined with that of the independent Lothian Birth Cohort 1921 (n = 517) in a meta-analysis. CONCLUSIONS: Increased polygenic risk of schizophrenia is associated with lower cognitive ability at age 70 and greater relative decline in general cognitive ability between the ages of 11 and 70. Common genetic variants may underlie both cognitive aging and risk of schizophrenia.

AB - BACKGROUND: Genome-wide association studies (GWAS) have shown a polygenic component to the risk of schizophrenia. The disorder is associated with impairments in general cognitive ability that also have a substantial genetic contribution. No study has determined whether cognitive impairments can be attributed to schizophrenia's polygenic architecture using data from GWAS. METHODS: Members of the Lothian Birth Cohort 1936 (LBC1936, n = 937) were assessed using the Moray House Test at age 11 and with the Moray House Test and a further cognitive battery at age 70. To create polygenic risk scores for schizophrenia, we obtained data from the latest GWAS of the Psychiatric GWAS Consortium on Schizophrenia. Schizophrenia polygenic risk profile scores were calculated using information from the Psychiatric GWAS Consortium on Schizophrenia GWAS. RESULTS: In LBC1936, polygenic risk for schizophrenia was negatively associated with IQ at age 70 but not at age 11. Greater polygenic risk for schizophrenia was associated with more relative decline in IQ between these ages. These findings were maintained when the results of LBC1936 were combined with that of the independent Lothian Birth Cohort 1921 (n = 517) in a meta-analysis. CONCLUSIONS: Increased polygenic risk of schizophrenia is associated with lower cognitive ability at age 70 and greater relative decline in general cognitive ability between the ages of 11 and 70. Common genetic variants may underlie both cognitive aging and risk of schizophrenia.

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DO - 10.1016/j.biopsych.2013.01.011

M3 - Article

C2 - 23419543

VL - 73

SP - 938

EP - 943

JO - Biological Psychiatry

JF - Biological Psychiatry

IS - 10

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Polygenic Risk for Schizophrenia Is Associated with Cognitive Change Between Childhood and Old Age

Abstract

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Projects

Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2.

RA2661 Centre for Cognitive Ageing and Cognitive Epidemiology Phase 2. Main Budget.

A Hundred at Ninety: the common cause Hypothesis of Ageing tested in four waves of the Lothian Birth Cohort 1921

Cite this