Biology subjects

Michel G Nivard

Publications and source records attributed to Michel G Nivard.

3 recordsLinked to original sources

bioRxiv2016

Ultra-rare disruptive and damaging mutations influence educational attainment in the general population

Ultra-rare inherited and de novo disruptive variants in highly constrained (HC) genes are enriched in neurodevelopmental disorders 1-5. However, their impact on cognition in the general population has not been explored. We hypothesize that disruptive and damaging ultra-rare variants (URVs) in HC genes not only confer risk to neurodevelopmental disorders, but also influence general cognitive abilities measured indirectly by years of education (YOE). We tested this hypothesis in 14,133 individuals with whole exome or genome sequencing data. The presence of one or more URVs was associated with a decrease in YOE (3.1 months less for each additional mutation; P-value=3.3x10-8) and the effect was stronger in HC genes enriched for brain expression (6.5 months less, P-value=3.4x10-5). The effect of these variants was more pronounced than the estimated effects of runs of homozygosity and pathogenic copy number variation 6-9. Our findings suggest that effects of URVs in HC genes are not confined to severe neurodevelopmental disorder, but influence the cognitive spectrum in the general population

Genetics↗

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↗