@article{whalleyhc2016,
title = {Dissection of major depressive disorder using polygenic risk scores for schizophrenia in two independent cohorts},
author = {Whalley, H. C.
Adams, M. J.
Hall, L. S.
Clarke, T. K.
Fernandez-Pujals, A. M.
Gibson, J.
Wigmore, E.
Hafferty, J.
Hagenaars, S. P.
Davies, G.
Campbell, A.
Hayward, C.
Lawrie, S. M.
Porteous, D. J.
Deary, I. J.
McIntosh, A. M.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27801894},
year = {2016},
date = {2016-11-02},
journal = {Transl Psychiatry},
abstract = {Major depressive disorder (MDD) is known for its substantial clinical and suspected causal heterogeneity. It is characterized by low mood, psychomotor slowing and increased levels of the personality trait neuroticism; factors also associated with schizophrenia (SCZ). It is possible that some cases of MDD may have a substantial genetic loading for SCZ. The presence of SCZ-like MDD subgroups would be indicated by an interaction between MDD status and polygenic risk of SCZ on cognitive, personality and mood measures. Here, we hypothesized that higher SCZ polygenic risk would define larger MDD case-control differences in cognitive ability, and smaller differences in distress and neuroticism. Polygenic risk scores (PRSs) for SCZ and their association with cognitive variables, neuroticism, mood and psychological distress were estimated in a large population-based cohort (Generation Scotland: Scottish Family Health Study, GS:SFHS). The individuals were divided into those with, and without, depression (n=2587 and n=16 764, respectively) to test for the interactions between MDD status and schizophrenia risk. Replication was sought in UK Biobank (UKB; n=6049 and n=27 476 cases and controls, respectively). In both the cohorts, we found significant interactions between SCZ-PRS and MDD status for measures of psychological distress (betaGS=-0.04, PGS=0.014 and betaUKB=-0.09, PUKB0.001 for GS:SFHS and UKB, respectively) and neuroticism (betaGS=-0.04, PGS=0.002 and betaUKB=-0.06, PUKB=0.023). In both the cohorts, there was a reduction of case-control differences on a background of higher genetic risk of SCZ. These findings suggest that depression on a background of high genetic risk for SCZ may show attenuated associations with distress and neuroticism. This may represent a causally distinct form of MDD more closely related to SCZ.},
keywords = {Depressive disorder, schizophrenia},
pubstate = {published},
tppubtype = {article}
}

@article{MehtaD2016,
title = {Evidence for Genetic Overlap Between Schizophrenia and Age at First Birth in Women},
author = {Mehta, Divya
Tropf, Felix C.
Gratten, Jacob
Bakshi, Andrew
Zhu, Zhihong
Bacanu, Silviu-Alin
Hemani, Gibran
Magnusson, Patrik K. E.
Barban, Nicola
Esko, Tonu
Metspalu, Andres
Snieder, Harold
Mowry, Bryan J.
Kendler, Kenneth S.
Yang, Jian
Visscher, Peter M.
McGrath, John J.
Mills, Melinda C.
Wray, Naomi R.
Lee, S. Hong
Psychiat Genomics, Consortium
LifeLines Cohort, Study
TwinsUk,},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27007234},
year = {2016},
date = {2016-05-01},
journal = {JAMA Psychiatry},
abstract = {IMPORTANCE A recently published study of national data by McGrath et al in 2014 showed increased risk of schizophrenia (SCZ) in offspring associated with both early and delayed parental age, consistent with a U-shaped relationship. However, it remains unclear if the risk to the child is due to psychosocial factors associated with parental age or if those at higher risk for SCZ tend to have children at an earlier or later age.OBJECTIVE To determine if there is a genetic association between SCZ and age at first birth (AFB) using genetically informative but independently ascertained data sets.DESIGN, SETTING, AND PARTICIPANTS This investigation used multiple independent genome-wide association study data sets. The SCZ sample comprised 18 957 SCZ cases and 22 673 controls in a genome-wide association study from the second phase of the Psychiatric Genomics Consortium, and the AFB sample comprised 12 247 genotyped women measured for AFB from the following 4 community cohorts: Estonia (Estonian Genome Center Biobank, University of Tartu), the Netherlands (LifeLines Cohort Study), Sweden (Swedish Twin Registry), and the United Kingdom (TwinsUK). Schizophrenia genetic risk for each woman in the AFB community sample was estimated using genetic effects inferred from the SCZ genome-wide association study.MAIN OUTCOMES AND MEASURES We tested if SCZ genetic risk was a significant predictor of response variables based on published polynomial functions that described the relationship between maternal age and SCZ risk in offspring in Denmark. We substituted AFB for maternal age in these functions, one of which was corrected for the age of the father, and found that the fit was superior for the model without adjustment for the father's age.RESULTS We observed a U-shaped relationship between SCZ risk and AFB in the community cohorts, consistent with the previously reported relationship between SCZ risk in offspring and maternal age when not adjusted for the age of the father. We confirmed that SCZ risk profile scores significantly predicted the response variables (coefficient of determination R-2 = 1.1E-03, P = 4.1E-04), reflecting the published relationship between maternal age and SCZ risk in offspring byMcGrath et al in 2014.CONCLUSIONS AND RELEVANCE This study provides evidence for a significant overlap between genetic factors associated with risk of SCZ and genetic factors associated with AFB. It has been reported that SCZ risk associated with increased maternal age is explained by the age of the father and that de novo mutations that occur more frequently in the germline of older men are the underlying causal mechanism. This explanation may need to be revised if, as suggested herein and if replicated in future studies, there is also increased genetic risk of SCZ in older mothers.},
keywords = {first birth, overlap, schizophrenia},
pubstate = {published},
tppubtype = {article}
}