Polygenic risk for schizophrenia and measured domains of cognition in individuals with psychosis and controls

Rebecca Shafee; Pranav Nanda; Jaya L Padmanabhan; Neeraj Tandon; Ney Alliey-Rodriguez; Sreeja Kalapurakkel; Daniel J Weiner; Raquel E Gur; Richard S E Keefe; Scot K Hill; Jeffrey R Bishop; Brett A Clementz; Carol A Tamminga; Elliot S Gershon; Godfrey D Pearlson; Matcheri S Keshavan; John A Sweeney; Steven A McCarroll; Elise B Robinson

doi:10.1038/s41398-018-0124-8

Polygenic risk for schizophrenia and measured domains of cognition in individuals with psychosis and controls

Transl Psychiatry. 2018 Apr 12;8(1):78. doi: 10.1038/s41398-018-0124-8.

Authors

Rebecca Shafee^{1

2}, Pranav Nanda³, Jaya L Padmanabhan⁴, Neeraj Tandon⁵, Ney Alliey-Rodriguez⁶, Sreeja Kalapurakkel^{7

8

9}, Daniel J Weiner^{7

8

9

10}, Raquel E Gur¹¹, Richard S E Keefe¹², Scot K Hill¹³, Jeffrey R Bishop^{14

15}, Brett A Clementz¹⁶, Carol A Tamminga¹⁷, Elliot S Gershon^{6

18}, Godfrey D Pearlson¹⁹, Matcheri S Keshavan²⁰, John A Sweeney²¹, Steven A McCarroll^{22

7

8}, Elise B Robinson^{7

8

9

23}

Affiliations

¹ Department of Genetics, Harvard Medical School, Boston, MA, USA. [email protected].
² Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. [email protected].
³ College of Physicians & Surgeons, Columbia University Medical Center, New York, NY, USA.
⁴ Department of Psychiatry and Cognitive Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁵ Baylor College of Medicine, Texas Medical Center, Houston, TX, USA.
⁶ Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
⁷ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁸ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁹ Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
¹⁰ Harvard Medical School, Boston, MA, USA.
¹¹ Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
¹² Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
¹³ Department of Psychology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA.
¹⁴ Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA.
¹⁵ Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
¹⁶ Department of Psychology and Neuroscience, University of Georgia, Athens, GA, USA.
¹⁷ Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA.
¹⁸ Department of Human Genetics, University of Chicago, Chicago, IL, USA.
¹⁹ Departments of Psychiatry and Neurobiology, Yale University and Olin Neuropsychiatric Research Center, Hartford, CT, USA.
²⁰ Department of Psychiatry, Beth Israel Deaconess Medical Center and Massachusetts Mental Health Center, Harvard Medical School, Boson, MA, USA.
²¹ Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.
²² Department of Genetics, Harvard Medical School, Boston, MA, USA.
²³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Abstract

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 (PRS_SCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BACS) that is greatly reduced in psychotic disorder patients, a measure of premorbid intelligence that is minimally affected by psychosis onset (the Wide-Range Achievement Test, WRAT); and educational attainment (EY), which covaries with both BACS and WRAT. Using genome-wide single nucleotide polymorphism (SNP) data from 314 psychotic and 423 healthy research participants in the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) Consortium, we investigated the association of PRS_SCZ with BACS, WRAT, and EY. Among apparently healthy individuals, greater genetic risk for schizophrenia (PRS_SCZ) was significantly associated with lower BACS scores (r = -0.17, p = 6.6 × 10^-4 at P_T = 1 × 10^-4), but not with WRAT or EY. Among individuals with psychosis, PRS_SCZ did not associate with variations in any of these three phenotypes. We further investigated the association between PRS_SCZ and WRAT in more than 4500 healthy subjects from the Philadelphia Neurodevelopmental Cohort. The association was again null (p > 0.3, N = 4511), suggesting that different cognitive phenotypes vary in their etiologic relationship with schizophrenia.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cognition
Female
Genetic Predisposition to Disease*
Humans
Male
Middle Aged
Multifactorial Inheritance*
Neuropsychological Tests
Polymorphism, Single Nucleotide
Psychotic Disorders / complications
Psychotic Disorders / genetics*
Risk Factors
Schizophrenia / complications
Schizophrenia / genetics*
Schizophrenic Psychology*

Abstract

Publication types

MeSH terms

Grants and funding