Identification of schizophrenia-associated loci by combining DNA methylation and gene expression data from whole blood

Eijk, Kristel R. van; Jong, Simone de; Strengman, Eric; Buizer-Voskamp, Jacobine E.; Kahn, René S.; Boks, Marco P.; Horvath, Steve; Ophoff, Roel A.

doi:10.1038/ejhg.2014.245

Cited by 46 publications

(31 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies range between investigation of Autism (e.g. [67]), to depression [68,69], anorexia [68], suicidality [70] or schizophrenia [71]. The considerable interest in use of this approach in the study of Alzheimer's disease has been largely spurred by the prospect of the development of a predictive blood transcriptomic diagnostic test [72][73][74].…”

Section: Blood Transcriptome Profiling Studies In Health and Diseasementioning

confidence: 99%

Assessment of immune status using blood transcriptomics and potential implications for global health

Chaussabel¹

2015

Seminars in Immunology

103

View full text Add to dashboard Cite

The immune system plays a key role in health maintenance and pathogenesis of a wide range of diseases. Leukocytes that are present in the blood convey valuable information about the status of the immune system. Blood transcriptomics, which consists in profiling blood transcript abundance on genome-wide scales, has gained in popularity over the past several years. Indeed, practicality and simplicity largely makes up for what this approach may lack in terms of cell population-level resolution. An extensive survey of the literature reveals increasingly widespread use across virtually all fields of medicine as well as across a number of different animal species, including model organisms but also animals of economical importance. Dissemination across such a wide range of disciplines holds the promise of adding a new perspective, breadth or context, to the considerable depth afforded by whole genome profiling of blood transcript abundance. Indeed, it is only through such contextualization that a truly global perspective will be gained from the use of systems approaches. Also discussed are opportunities that may arise for the fields of immunology and medicine from using blood transcriptomics as a common denominator for developing interactions and cooperation across fields of research that have traditionally been and largely remain compartmentalized. Finally, an argument is made for building immunology research capacity using blood transcriptomics platforms in low-resource and high-disease burden settings.

show abstract

Section: Blood Transcriptome Profiling Studies In Health and Diseasementioning

confidence: 99%

Assessment of immune status using blood transcriptomics and potential implications for global health

Chaussabel¹

2015

Seminars in Immunology

103

View full text Add to dashboard Cite

show abstract

“…Post-GWAS studies of complex disorders are increasingly integrating these methylomics analyses, not only with the GWAS signals themselves but also with eQTL and regulatory-region (e.g. enhancer) maps, in order to uncover functional risk variants -including ones that may be involved in brain function and/or psychiatric disorders (Clark et al 2015;Gamazon et al 2013;Gibbs et al 2010;Kumar et al 2015;van Eijk et al 2015;Wockner et al 2014;Zhao et al 2014).…”

Section: Dna Methylome Mapsmentioning

confidence: 99%

Decoding the non‐coding genome: elucidating genetic risk outside the coding genome

Barr

Misener

2016

Genes Brain and Behavior

View full text Add to dashboard Cite

Current evidence emerging from genome-wide association studies indicates that the genetic underpinnings of complex traits are likely attributable to genetic variation that changes gene expression, rather than (or in combination with) variation that changes protein-coding sequences. This is particularly compelling with respect to psychiatric disorders, as genetic changes in regulatory regions may result in differential transcriptional responses to developmental cues and environmental/psychosocial stressors. Until recently, however, the link between transcriptional regulation and psychiatric genetic risk has been understudied. Multiple obstacles have contributed to the paucity of research in this area, including challenges in identifying the positions of remote (distal from the promoter) regulatory elements (e.g. enhancers) and their target genes and the underrepresentation of neural cell types and brain tissues in epigenome projects -the availability of high-quality brain tissues for epigenetic and transcriptome profiling, particularly for the adolescent and developing brain, has been limited. Further challenges have arisen in the prediction and testing of the functional impact of DNA variation with respect to multiple aspects of transcriptional control, including regulatory-element interaction (e.g. between enhancers and promoters), transcription factor binding and DNA methylation. Further, the brain has uncommon DNA-methylation marks with unique genomic distributions not found in other tissues -current evidence suggests the involvement of non-CG methylation and 5-hydroxymethylation in neurodevelopmental processes but much remains unknown. We review here knowledge gaps as well as both technological and resource obstacles that will need to be overcome in order to elucidate the involvement of brain-relevant gene-regulatory variants in genetic risk for psychiatric disorders. Keywords:5-Hydroxymethylation, adolescent brain, enhancers, epigenetics, gene expression, gene regulation, methylation, non-CG methylation, non-coding RNA, psychiatric disorders, transcriptome Received 7 August 2015, revised 19 October 2015, accepted for publication 28 October 2015Changes in gene expression are now acknowledged as a major contributor to the genetic risk for complex genetic traits. In this article, we review the key evidence supporting this, as well as mechanisms by which DNA variation influences gene expression and methodologies for studying these relationships. We note that a comprehensive review of the genetic findings for psychiatric disorders is beyond the scope of this review, as is a comprehensive review of epigenetic regulation. Instead, we focus this review on classes of transcripts and epigenetic marks that are prevalent in brain and that may make unique contributions to brain function. We also focus on methods that, in our opinion, are likely to make the greatest contributions to moving the field forward. Finally, we outline a number of obstacles that currently stand in the way of fully elucidating the relationships b...

show abstract

“…Notably, three significant associations included migraine index SNP at the YAP1, REST, and ZCCHC14 loci. This finding is consistent with previous reports of mQTL enrichment of top susceptibility variants from GWAS in whole blood (130,150,307). However, we did not find overlap between mQTLs and eQTLs or evidence for differential methylation of the associated CpG sites and therefore cannot draw conclusions on a potential functional mechanism.…”

Section: Discussionsupporting

confidence: 81%

Integrating Genome-Wide Association and Blood Genomic Profiling Data to Characterise Migraine Risk Loci

Gerring¹

View full text Add to dashboard Cite

Migraine is a frequent, debilitating and painful headache disorder that normally affects people during their most productive years of life (25% of females and 8% of males).Genome-wide association studies have identified 44 independent single nucleotide polymorphisms associated with migraine, however the causal genes and pathogenic mechanisms underlying the disorder remain unknown. Therefore, we performed a multi-staged integrated study of gene expression and DNA methylation in a large sample of migraine cases and non-migraine controls from the Brisbane Systems Genetics Study. We identified several gene expression networks and differentially methylated regions associated with migraine, which were subsequently characterised using robust statistical and pathway-based approaches. Integration of existing genomewide association data with gene expression and methylation data prioritised migraine susceptibility genes for further functional characterisation. This study suggests the use of multiple molecular data to study existing migraine loci has the potential to provide a substantial contribution to understanding the underlying genetic architecture and biological mechanisms of migraine, and may help in the development of diagnostic tests and new targets for drug therapy.3

show abstract

Identification of schizophrenia-associated loci by combining DNA methylation and gene expression data from whole blood

Cited by 46 publications

References 24 publications

Assessment of immune status using blood transcriptomics and potential implications for global health

Assessment of immune status using blood transcriptomics and potential implications for global health

Decoding the non‐coding genome: elucidating genetic risk outside the coding genome

Integrating Genome-Wide Association and Blood Genomic Profiling Data to Characterise Migraine Risk Loci

Contact Info

Product

Resources

About