@article{eda420eb32874168a98ea59cf92b48c2,
title = "Molecular genetic evidence for overlap between general cognitive ability and risk for schizophrenia: A report from the Cognitive Genomics consorTium (COGENT)",
abstract = "It has long been recognized that generalized deficits in cognitive ability represent a core component of schizophrenia (SCZ), evident before full illness onset and independent of medication. The possibility of genetic overlap between risk for SCZ and cognitive phenotypes has been suggested by the presence of cognitive deficits in first-degree relatives of patients with SCZ; however, until recently, molecular genetic approaches to test this overlap have been lacking. Within the last few years, large-scale genome-wide association studies (GWAS) of SCZ have demonstrated that a substantial proportion of the heritability of the disorder is explained by a polygenic component consisting of many common single-nucleotide polymorphisms (SNPs) of extremely small effect. Similar results have been reported in GWAS of general cognitive ability. The primary aim of the present study is to provide the first molecular genetic test of the classic endophenotype hypothesis, which states that alleles associated with reduced cognitive ability should also serve to increase risk for SCZ. We tested the endophenotype hypothesis by applying polygenic SNP scores derived from a large-scale cognitive GWAS meta-analysis (∼5000 individuals from nine nonclinical cohorts comprising the Cognitive Genomics consorTium (COGENT)) to four SCZ case-control cohorts. As predicted, cases had significantly lower cognitive polygenic scores compared to controls. In parallel, polygenic risk scores for SCZ were associated with lower general cognitive ability. In addition, using our large cognitive meta-analytic data set, we identified nominally significant cognitive associations for several SNPs that have previously been robustly associated with SCZ susceptibility. Results provide molecular confirmation of the genetic overlap between SCZ and general cognitive ability, and may provide additional insight into pathophysiology of the disorder.",
author = "T. Lencz and E. Knowles and G. Davies and S. Guha and Liewald, {D. C.} and Starr, {J. M.} and S. Djurovic and I. Melle and K. Sundet and A. Christoforou and I. Reinvang and S. Mukherjee and Pamela Derosse and A. Lundervold and Steen, {V. M.} and M. John and T. Espeseth and K. R{\"a}ikk{\"o}nen and E. Widen and A. Palotie and Eriksson, {J. G.} and I. Giegling and B. Konte and M. Ikeda and P. Roussos and S. Giakoumaki and Burdick, {K. E.} and A. Payton and W. Ollier and M. Horan and G. Donohoe and D. Morris and A. Corvin and M. Gill and N. Pendleton and N. Iwata and A. Darvasi and P. Bitsios and D. Rujescu and J. Lahti and Hellard, {S. L.} and Keller, {M. C.} and Andreassen, {O. A.} and Deary, {I. J.} and Glahn, {D. C.} and Malhotra, {A. K.}",
note = "Funding Information: This work has been supported by grants from the National Institutes of Health (R01 MH079800 and P50 MH080173 to AKM; RC2 MH089964 to TL; R01 MH080912 to DCG; K23 MH077807 to KEB; K01 MH085812 to MCK). Dr Donohoe is generously funded by the Health Research Board (Ireland) and Science Foundation Ireland. Data collection for the TOP cohort was supported by the Research Council of Norway, South-East Norway Health Authority. The NCNG study was supported by Research Council of Norway Grants 154313/V50 and 177458/V50. The NCNG GWAS was financed by grants from the Bergen Research Foundation, the University of Bergen, the Research Council of Norway (FUGE, Psykisk Helse), Helse Vest RHF and Dr Einar Martens Fund. The Helsinki Birth Cohort Study has been supported by grants from the Academy of Finland, the Finnish Diabetes Research Society, Folkh{\"a}lsan Research Foundation, Novo Nordisk Foundation, Finska L{\"a}kares{\"a}llskapet, Signe and Ane Gyllenberg Foundation, University of Helsinki, Ministry of Education, Ahokas Foundation, Emil Aaltonen Foundation. For the LBC cohort, phenotype collection was supported by Research Into Ageing (continues as part of Age UK The Disconnected Mind project). Genotyping was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC). The work was undertaken by The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (G0700704/84698). Funding from the BBSRC, Engineering and Physical Sciences Research Council (EPSRC), Economic and Social Research Council (ESRC), and MRC is gratefully acknowledged. We are grateful to investigators, led by Pablo Gejman, who have made data for the MGS cohort publicly available through dbGAP (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study. cgi?study_id=phs000167.v1.p1; /cgi-bin/study.cgi?study_id=phs000021.v2.p1).",
year = "2014",
month = feb,
doi = "10.1038/mp.2013.166",
language = "English",
volume = "19",
pages = "168--174",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Springer Nature",
number = "2",
}
