RT Journal Article
SR Electronic
T1 Effects of autozygosity and schizophrenia polygenic risk on cognitive and brain developmental trajectories
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 159939
DO 10.1101/159939
A1 Aldo Cordova-Palomera
A1 Tobias Kaufmann
A1 Francesco Bettella
A1 Yunpeng Wang
A1 Nhat Trung Doan
A1 Dennis van der Meer
A1 Dag Alnæs
A1 Jaroslav Rokicki
A1 Torgeir Moberget
A1 Ida Elken Sønderby
A1 Ole A. Andreassen
A1 Lars T. Westlye
YR 2017
UL http://biorxiv.org/content/early/2017/07/05/159939.abstract
AB Cognitive and brain development are determined by dynamic interactions between genes and environment across the lifespan. Aside from marker-by-marker analyses of polymorphisms, biologically meaningful features of the whole-genome (derived from the combined effect of individual markers) have been postulated to inform on human phenotypes including cognitive traits and their underlying biological substrate.Here, estimates of inbreeding and schizophrenia genetic susceptibility calculated from genome-wide data –runs of homozygosity (ROH) and schizophrenia polygenic risk score (PGRS)– are analyzed in relation to cognitive and brain development in a general-population sample of 4,183 European-ancestry participants aged 8-22, from the Philadelphia Neurodevelopmental Cohort.The findings suggest that a higher ROH burden and higher schizophrenia PGRS are associated with increased intelligence, both independently and in interaction (ROH PGRS). Cognition~ROH and cognition~PGRS associations are in line with previous reports, and may respectively evidence that assortative mating influences intelligence, and that individuals with high schizophrenia genetic risk who do not transition to disease status are cognitively resilient. Additionally, ROH × PGRS significant interaction effects indicate that more inbred individuals are more likely to display higher cognitive test scores in the presence of high schizophrenia polygenic risk score.Neuroanatomical data from a subset of 516 individuals showed that the effects of schizophrenia PGRS on cognition could be modulated by brain structure, although larger imaging datasets are needed to accurately disentangle the underlying neural mechanisms linking IQ with both inbreeding and the genetic burden for schizophrenia.