TY - JOUR
T1 - Investigation of the genetic association between quantitative measures of psychosis and schizophrenia
T2 - A polygenic risk score analysis
AU - The Schizophrenia Psychiatric Genomic Consortium
AU - Derks, Eske M.
AU - Vorstman, Jacob A.S.
AU - Ripke, Stephan
AU - Kahn, Rene S.
AU - Ophoff, Roel A.
AU - O'Donovan, Michael C.
AU - Craddock, Nicholas
AU - Holmans, Peter A.
AU - Hamshere, Marian
AU - Williams, Hywel J.
AU - Moskvina, Valentina
AU - Dwyer, Sarah
AU - Georgieva, Lyudmila
AU - Zammit, Stan
AU - Owen, Michael J.
AU - Sullivan, Patrick F.
AU - Lin, Dan Yu
AU - van den Oord, Edwin
AU - Kim, Yunjung
AU - Scott Stroup, T.
AU - Lieberman, Jeffrey A.
AU - St Clair, David
AU - Kirov, George K.
AU - Nikolov, Ivan
AU - Toncheva, Draga
AU - Milanova, Vihra
AU - Morris, Derek W.
AU - O'Dushlaine, Colm T.
AU - Kenny, Elaine
AU - Quinn, Emma M.
AU - Gill, Michael
AU - Corvin, Aiden
AU - Blackwood, Douglas H.R.
AU - McGhee, Kevin A.
AU - Pickard, Ben
AU - Malloy, Pat
AU - Maclean, Alan W.
AU - McIntosh, Andrew
AU - McQuillin, Andrew
AU - Choudhury, Khalid
AU - Datta, Susmita
AU - Pimm, Jonathan
AU - Thirumalai, Srinivasa
AU - Puri, Vinay
AU - Krasucki, Robert
AU - Lawrence, Jacob
AU - Quested, Digby
AU - Bass, Nicholas
AU - Gurling, Hugh
AU - Pato, Michele T.
AU - Pato, Carlos N.
AU - Fanous, Ayman
AU - Hultman, Christina M.
AU - Lichtenstein, Paul
AU - Bergen, Sarah E.
AU - Scolnick, Edward
AU - Sklar, Pamela
AU - Gejman, Pablo V.
AU - Sanders, Alan R.
AU - Duan, Jubao
AU - Levinson, Douglas F.
AU - Shi, Jianxin
AU - Buccola, Nancy G.
AU - Mowry, Bryan J.
AU - Freedman, Robert
AU - Amin, Farooq
AU - Black, Donald W.
AU - Silverman, Jeremy M.
AU - Byerley, William F.
AU - Robert Cloninger, C.
AU - Cichon, Sven
AU - Rietschel, Marcella
AU - Nöthen, Markus M.
AU - Maier, Wolfgang
AU - Schulze, Thomas G.
AU - Mattheisen, Manuel
AU - Hansen, Thomas
AU - Olsen, Line
AU - Ingason, Andrés
AU - Jakobsen, Klaus D.
AU - Schmock, Henriette
AU - Skjødt, Celina
AU - Rosengren, Anders
AU - Høffding, Louise K.E.
AU - Thygersen, Johan H.
AU - Vangkilde, Anders
AU - Werge, Thomas
AU - Giegling, Ina
AU - Hartmann, Annette M.
AU - Konnerth, Heike
AU - Friedl, Marion
AU - Konte, Bettina
AU - Muglia, Pierandrea
AU - Rujescu, Dan
AU - Djurovic, Srdjan
AU - Mattingsdal, Morten
AU - Agartz, Ingrid
AU - Melle, Ingrid
AU - Andreassen, Ole A.
AU - Cantor, Rita M.
PY - 2012/6/22
Y1 - 2012/6/22
N2 - The presence of subclinical levels of psychosis in the general population may imply that schizophrenia is the extreme expression of more or less continuously distributed traits in the population. In a previous study, we identified five quantitative measures of schizophrenia (positive, negative, disorganisation, mania, and depression scores). The aim of this study is to examine the association between a direct measure of genetic risk of schizophrenia and the five quantitative measures of psychosis. Estimates of the log of the odds ratios of case/control allelic association tests were obtained from the Psychiatric GWAS Consortium (PGC) (minus our sample) which included genome-wide genotype data of 8,690 schizophrenia cases and 11,831 controls. These data were used to calculate genetic risk scores in 314 schizophrenia cases and 148 controls from the Netherlands for whom genotype data and quantitative symptom scores were available. The genetic risk score of schizophrenia was significantly associated with case-control status (p<0.0001). In the case-control sample, the five psychosis dimensions were found to be significantly associated with genetic risk scores; the correlations ranged between.15 and.27 (all p<.001). However, these correlations were not significant in schizophrenia cases or controls separately. While this study confirms the presence of a genetic risk for schizophrenia as categorical diagnostic trait, we did not find evidence for the genetic risk underlying quantitative schizophrenia symptom dimensions. This does not necessarily imply that a genetic basis is nonexistent, but does suggest that it is distinct from the polygenic risk score for schizophrenia.
AB - The presence of subclinical levels of psychosis in the general population may imply that schizophrenia is the extreme expression of more or less continuously distributed traits in the population. In a previous study, we identified five quantitative measures of schizophrenia (positive, negative, disorganisation, mania, and depression scores). The aim of this study is to examine the association between a direct measure of genetic risk of schizophrenia and the five quantitative measures of psychosis. Estimates of the log of the odds ratios of case/control allelic association tests were obtained from the Psychiatric GWAS Consortium (PGC) (minus our sample) which included genome-wide genotype data of 8,690 schizophrenia cases and 11,831 controls. These data were used to calculate genetic risk scores in 314 schizophrenia cases and 148 controls from the Netherlands for whom genotype data and quantitative symptom scores were available. The genetic risk score of schizophrenia was significantly associated with case-control status (p<0.0001). In the case-control sample, the five psychosis dimensions were found to be significantly associated with genetic risk scores; the correlations ranged between.15 and.27 (all p<.001). However, these correlations were not significant in schizophrenia cases or controls separately. While this study confirms the presence of a genetic risk for schizophrenia as categorical diagnostic trait, we did not find evidence for the genetic risk underlying quantitative schizophrenia symptom dimensions. This does not necessarily imply that a genetic basis is nonexistent, but does suggest that it is distinct from the polygenic risk score for schizophrenia.
UR - https://www.scopus.com/pages/publications/84862667477
U2 - 10.1371/journal.pone.0037852
DO - 10.1371/journal.pone.0037852
M3 - Article
SN - 1932-6203
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e37852
ER -