Effects of a neurodevelopmental genes based polygenic risk score for schizophrenia and single gene variants on brain structure in non-clinical subjects: A preliminary report

Published on Oct 1, 2019in Schizophrenia Research4.569
· DOI :10.1016/j.schres.2019.07.061
Robert Spalthoff3
Estimated H-index: 3
Franziska Degenhardt32
Estimated H-index: 32
(University of Bonn)
+ 6 AuthorsIgor Nenadic23
Estimated H-index: 23
(Phillips University)
Abstract We tested whether a polygenic risk score integrating the effects of genes affecting neurodevelopment is associated to brain structural variation in healthy subjects. We acquired magnetic resonance imaging and genetic data of 167 healthy adults and computed a neurodevelopmental polygenic risk score (nPRS). We correlated the nPRS with local gyrification, cortical thickness and grey matter density and explored effects of single nucleotide polymorphisms included in the score. We did not find significant correlations of this nPRS with either measure. Individuals with the risk allele at rs11139497 show increases in cortical thickness (p
  • References (19)
  • Citations (0)
📖 Papers frequently viewed together
47 Citations
2 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
#1Antonio F. Pardiñas (Cardiff University)H-Index: 12
#2Peter Holmans (Cardiff University)H-Index: 94
Last. James T.R. Walters (Cardiff University)H-Index: 37
view all 69 authors...
Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 1...
219 CitationsSource
#1Rikke Hilker (UCPH: University of Copenhagen)H-Index: 4
#2Dorte Helenius (Lundbeck)H-Index: 2
Last. Birte Glenthøj (UCPH: University of Copenhagen)H-Index: 37
view all 8 authors...
Abstract Background Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology. Methods Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951...
56 CitationsSource
#1S. Van der Auwera (German Center for Neurodegenerative Diseases)H-Index: 3
#2Katharina Wittfeld (German Center for Neurodegenerative Diseases)H-Index: 20
Last. H.J. Grabe (German Center for Neurodegenerative Diseases)H-Index: 9
view all 13 authors...
Schizophrenia is associated with brain structural abnormalities including gray and white matter volume reductions. Whether these alterations are caused by genetic risk variants for schizophrenia is unclear. Previous attempts to detect associations between polygenic factors for schizophrenia and structural brain phenotypes in healthy subjects have been negative or remain non-replicated. In this study, we used genetic risk scores that were based on the accumulated effect of selected risk variants ...
5 CitationsSource
#1Lianne M. Reus (Edin.: University of Edinburgh)H-Index: 5
#2Xueyi ShenH-Index: 7
Last. Andrew M. McIntosh (Edin.: University of Edinburgh)H-Index: 75
view all 13 authors...
Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank
27 CitationsSource
#1Susanne Erk (Charité)H-Index: 17
#2Sebastian Mohnke (Charité)H-Index: 15
Last. Henrik Walter (Charité)H-Index: 60
view all 22 authors...
Recently, 125 loci with genome-wide support for association with schizophrenia were identified. We investigated the impact of these variants and their accumulated genetic risk on brain activation in five neurocognitive domains of the Research Domain Criteria (working memory, reward processing, episodic memory, social cognition and emotion processing). In 578 healthy subjects we tested for association (i) of a polygenic risk profile score (RPS) including all single-nucleotide polymorphisms (SNPs)...
14 CitationsSource
#1Bing LiuLingzhong FanYue (CAS: Chinese Academy of Sciences)H-Index: 24
#2Xiaolong Zhang (CAS: Chinese Academy of Sciences)H-Index: 7
Last. Tianzi JiangH-Index: 67
view all 8 authors...
Schizophrenia is highly heritable, whereas the effect of each genetic variant is very weak. Since clinical heterogeneity and complexity of schizophrenia is high, considerable effort has been made to relate genetic variants to underlying neurobiological aspects of schizophrenia (endophenotypes). Given the polygenic nature of schizophrenia, our goal was to form a measure of additive genetic risk and explore its relationship to cortical morphology. Utilizing the data from a recent genome-wide assoc...
27 CitationsSource
#1S. Van der Auwera (German Center for Neurodegenerative Diseases)H-Index: 17
#2Katharina Wittfeld (German Center for Neurodegenerative Diseases)H-Index: 20
Last. Hans J. Grabe (German Center for Neurodegenerative Diseases)H-Index: 60
view all 6 authors...
21 CitationsSource
#1Stephan Ripke (Broad Institute)H-Index: 74
#2Benjamin M. Neale (Broad Institute)H-Index: 85
Last. Michael O. Donovan (Cardiff University)H-Index: 122
view all 300 authors...
Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations wer...
3,480 CitationsSource
#1Deborah Cooper (Royal Edinburgh Hospital)H-Index: 3
#2Victoria Barker (Royal Edinburgh Hospital)H-Index: 5
Last. Stephen M. Lawrie (Royal Edinburgh Hospital)H-Index: 51
view all 5 authors...
Abstract Computational brain-imaging studies of individuals at familial high risk for psychosis have provided interesting results, but interpreting these findings can be a challenge due to a number of factors. We searched the literature for studies reporting whole brain voxel-based morphometry (VBM) or functional magnetic resonance imaging (fMRI) findings in people at familial high risk for schizophrenia compared with a control group. A voxel-wise meta-analysis with the effect-size version of Si...
64 CitationsSource
#1Robert Dahnke (FSU: University of Jena)H-Index: 11
#2Rachel Aine Yotter (FSU: University of Jena)H-Index: 14
Last. Christian Gaser (FSU: University of Jena)H-Index: 61
view all 3 authors...
Abstract Several properties of the human brain cortex, e.g., cortical thickness and gyrification, have been found to correlate with the progress of neuropsychiatric disorders. The relationship between brain structure and function harbors a broad range of potential uses, particularly in clinical contexts, provided that robust methods for the extraction of suitable representations of the brain cortex from neuroimaging data are available. One such representation is the computationally defined centr...
74 CitationsSource
Cited By0