Biology subjects

Jaffe, A.

Publications and source records attributed to Jaffe, A..

3 recordsLinked to original sources

bioRxiv2018

Association of a lincRNA postmortem with suicide by violent means and in vivo with aggressive phenotypes

ObjectivePrevious findings suggest that differences in brain expression of a human-specific long intergenic non-coding RNA (LINC01268; GRCh37/hg19: LOC285758) may be linked to aggressive behavior and suicide. The authors sought to replicate and extend these findings in a new sample, and translate the results to the behavioral level in living healthy subjects.\n\nMethodThe authors examined RNA sequencing data in human brain to confirm the prior postmortem association of the lincRNA specifically with suicide by violent means. In addition, they used a genetic variant associated with LINC01268 expression to detect association with in vivo prefrontal physiology related to behavioral control. They finally performed weighted gene co-expression network analysis (WGCNA) and gene-ontology analysis to identify biological processes associated with a LINC01268 co-expression network.\n\nResultsIn the replication sample, prefrontal expression of LINC01268 was again higher in suicides by violent means (N=65) than both non-suicides (N=78; 1.29e-06) and suicides by non-violent means (N=46; p=1.4e-06). In a living cohort, carriers of the minor allele of a SNP associated with increased LINC01268 expression in brain scored higher on a lifetime aggression questionnaire and show diminished engagement of prefrontal cortex (BA10) when viewing angry faces during fMRI. WGCNA highlighted the immune response.\n\nConclusionsThese results suggest that LINC01268 influences emotional regulation, aggressive behavior and suicide by violent means; the underlying biological dynamics may include modulation of genes potentially engaged in the immune response.

neuroscience↗

bioRxiv2017

Developmental effects of maternal smoking during pregnancy on the human frontal cortex transcriptome

Cigarette smoking during pregnancy is a major public health concern. While there are well-described consequences in early child development, there is very little known about the effects of maternal smoking on human cortical biology during prenatal life. We therefore performed a genome-wide differential gene expression analysis using RNA sequencing (RNA-seq) on prenatal (N=33; 16 smoking-exposed) as well as adult (N=207; 57 active smokers) human post-mortem prefrontal cortices. Smoking exposure during the prenatal period was directly associated with differential expression of 14 genes; in contrast, during adulthood, despite a much larger sample size, only 2 genes showed significant differential expression (FDR<10%). Moreover, 1,315 genes showed significantly different exposure effects between maternal smoking during pregnancy and direct exposure in adulthood (FDR<10%) - these differences were largely driven by prenatal differences that were enriched for pathways previously implicated in addiction and synaptic function. Furthermore, prenatal and age-dependent differentially expressed genes were enriched for genes implicated in non-syndromic autism spectrum disorder (ASD) and were differentially expressed as a set between patients with ASD and controls in post-mortem cortical regions. These results underscore the enhanced sensitivity to the biological effect of smoking exposure in the developing brain and offer novel insight into the effects of maternal smoking during pregnancy on the prenatal human brain. They also begin to address the relationship between in utero exposure to smoking and the heightened risks for the subsequent development of neuropsychiatric disorders.\n\nOne Sentence SummaryMaternal smoking during pregnancy alters the expression of genes within the developing human cortex and these changes are enriched for genes implicated in neuropsychiatric disorders.

neuroscience↗

bioRxiv2017

Correcting For Cell-Type Heterogeneity In Epigenome-Wide Association Studies: Premature Analyses And Conclusions

Recently, a study by Rahmani et al [1] claimed that a reference-free cell-type deconvolution method, called ReFACTor, leads to improved power and improved estimates of cell-type composition compared to competing reference-free and reference-based methods in the context of Epigenome-Wide Association Studies (EWAS). However, we identified many critical flaws (both conceptual and statistical in nature), which seriously question the validity of their claims. We outlined constructive criticism in a recent correspondence letter, Zheng et al [2]. The purpose of this letter is two-fold. First, to present additional analyses, which demonstrate that our original criticism is statistically sound. Second, to highlight additional serious concerns, which Rahmani et al have not yet addressed. In summary, we find that ReFACTor has not been demonstrated to outperform state-of-the-art reference-free methods such as SVA or RefFreeEWAS, nor state-of-the-art reference-based methods. Thus, the claim by Rahmani et al (a claim reiterated in their recent response letter [3]) that ReFACT or represents an advance over the state-of-the-art is not supported by an objective and rigorous statistical analysis of the data.

bioinformatics↗