Biology subjects

Raikkonen, K.

Publications and source records attributed to Raikkonen, K..

2 recordsLinked to original sources

bioRxiv2017

Large-Scale cognitive GWAS Meta-analysis Reveals Tissue-Specific Neural Expression and Potential Nootopic Drug Targets

Neurocognitive ability is a fundamental readout of brain function, and cognitive deficits are a critical component of neuropsychiatric disorders, yet neurocognition is poorly understood at the molecular level. In the present report, we present the largest genome-wide association studies (GWAS) of cognitive ability to date (N=107,207), and further enhance signal by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with cognitive ability, 34 of which were novel. A total of 350 genes were implicated, and this list showed significant enrichment for genes associated with Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis of gene results implicated the biological process of neurogenesis, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker; and LY97241, a potassium channel inhibitor. Transcriptome-wide analysis revealed that the implicated genes were strongly expressed in neurons, but not astrocytes or oligodendrocytes, and were more strongly associated with fetal brain expression than adult brain expression. Several tissue-specific gene expression relationships to cognitive ability were observed (for example, DAG1 levels in the hippocampus). Finally, we report novel genetic correlations between cognitive ability and disparate phenotypes such as maternal age at first birth and number of children, as well as several autoimmune disorders.

genomics↗

bioRxiv2017

An epigenome-wide association study of educational attainment (n = 10,767)

The epigenome has been shown to be influenced by biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption, and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here, we provide evidence on the associations between epigenetic modifications--in our case, CpG methylation--and educational attainment (EA), a biologically distal environmental factor that is arguably among of the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10,767 individuals. While we find that 9 CpG probes are significantly associated with EA, only two remain associated when we restrict the sample to never-smokers. These two are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, their effect sizes on EA are far smaller than the known associations between CpG probes and biologically proximal environmental factors. Two analyses that combine the effects of many probes--polygenic methylation score and epigenetic-clock analyses--both suggest small associations with EA. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

genetics↗