Biology subjects

Dorret I Boomsma

Publications and source records attributed to Dorret I Boomsma.

4 recordsLinked to original sources

bioRxiv2016

Genetic overlap between schizophrenia and developmental psychopathology: a longitudinal approach applied to common childhood disorders between age 7 and 15 years

Various non-psychotic psychiatric disorders in childhood and adolescence can precede the onset of schizophrenia, but the nature of this relationship remains unclear. We investigated to what extent the association between schizophrenia and psychiatric disorders in childhood is explained by shared genetic risk factors.\n\nPolygenic risk scores (PRS), reflecting an individuals genetic risk for schizophrenia, were constructed for participants in two birth cohorts (2,588 children from the Netherlands Twin Register (NTR) and 6,127 from the Avon Longitudinal Study of Parents And Children (ALSPAC)). The associations between schizophrenia PRS and measures of anxiety, depression, attention deficit hyperactivity disorder (ADHD), and oppositional defiant disorder/conduct disorder (ODD/CD) were estimated at age 7, 10, 12/13 and 15 years in the two cohorts. Results were then meta-analyzed, and age-effects and differences in the associations between disorders and PRS were formally tested in a meta-regression.\n\nThe schizophrenia PRS was associated with childhood and adolescent psychopathology Where the association was weaker for ODD/CD at age 7. The associations increased with age this increase was steepest for ADHD and ODD/CD. The results are consistent with a common genetic etiology of schizophrenia and developmental psychopathology as well as with a stronger shared genetic etiology between schizophrenia and adolescent onset psychopathology.\n\nA multivariate meta-analysis of multiple and repeated observations enabled to optimally use the longitudinal data across diagnoses in order to provide knowledge on how childhood disorders develop into severe adult psychiatric disorders.

Genetics↗

bioRxiv2015

GWIS: Genome Wide Inferred Statistics for non-linear functions of multiple phenotypes

Here we present a method of genome wide inferred study (GWIS) that provides an approximation of genome wide association study (GWAS) summary statistics for a variable that is a function of phenotypes for which GWAS summary statistics, phenotypic means and covariances are available. GWIS can be performed regardless of sample overlap between the GWAS of the phenotypes on which the function depends. As GWIS provides association estimates and their standard errors for each SNP, GWIS can form the basis for polygenic risk scoring, LD score regression1, Mendelian randomization studies, biological annotation and other analyses. Here, we replicate a body mass index (BMI) GWAS using GWIS based on a height GWAS and a weight GWAS. We proceed to use a GWIS to further our understanding of the genetic architecture of schizophrenia and bipolar disorder.

Genetics↗

bioRxiv2015

Integrative approaches for large-scale transcriptome-wide association studies

Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance levels of one or multiple proteins. In this work we introduce a powerful strategy that integrates gene expression measurements with large-scale genome-wide association data to identify genes whose cis-regulated expression is associated to complex traits. We use a relatively small reference panel of individuals for which both genetic variation and gene expression have been measured to impute gene expression into large cohorts of individuals and identify expression-trait associations. We extend our methods to allow for indirect imputation of the expression-trait association from summary association statistics of large-scale GWAS1-3. We applied our approaches to expression data from blood and adipose tissue measured in [~]3,000 individuals overall. We then imputed gene expression into GWAS data from over 900,000 phenotype measurements4-6 to identify 69 novel genes significantly associated to obesity-related traits (BMI, lipids, and height). Many of the novel genes were associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Overall our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits.

Genetics↗

bioRxiv2015

Life-span development of functional brain networks as assessed with minimum spanning tree analysis of resting state EEG.

The brain matures with large quantitative changes in anatomy and function. Graph analysis of EEG has previously revealed increased connectivity between distant brain areas and a decrease in randomness and increased integration in the brain network with concurrent increased modularity. Comparisons of graph parameters across age groups, however, may be confounded with network degree distributions. Here, we analyzed graph parameters from minimum spanning tree (MST) graphs. MST graphs are constructed by selecting only the strongest available connections avoiding loops resulting in a backbone graph that is thought reflect the major qualitative properties of connectivity while allowing a better comparison across age groups by avoiding the degree distribution confound. EEG was recorded in a large (N=1500) population-based sample aged 5 to 71 years. Connectivity was assessed using Phase Lag Index to reduce effects of volume conduction. As previously reported, connectivity increased from childhood to adolescence, continuing to grow nonsignificantly into adulthood decreasing only after ~30 years of age. Leaf number, degree, degree correlation, maximum centrality from the MST graph indicated a pattern of increased integration and decreased randomness from childhood into early adulthood. The observed development in network topology suggested that maturation at the neuronal level is aimed to increase connectivity as well as increase integration of the brain network. We confirm that brain network connectivity shows quantitative changes across the life span, and additionally demonstrate parallel qualitative changes in the connectivity pattern.

Neuroscience↗