Process genes list: An approach to link genetics and human brain imaging

Poblete, Guillermo; Gosnell, Savannah N.; Meyer, Matthew J.; Fang, Mary; Nguyen, Tien Dat; Patriquin, Michelle A.; Nielsen, David A.; Kosten, Thomas R.; Salas, Ramiro

doi:10.1016/j.jneumeth.2020.108695

Cited by 5 publications

(10 citation statements)

References 18 publications

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“…To evaluate the functions of the genes we found only in Sapiens further, we used Process Genes List to analyze lists of genes that mapped to particular SNP sets with at least one gene found only in Sapiens [97]. This machine learning method uses the Allen Brain Atlas to calculate a normalized average mRNA expression level in each brain region for lists of each gene set.…”

Section: Gene Co-expression In Brainmentioning

confidence: 99%

Evolution of genetic networks for human creativity

et al. 2021

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The genetic basis for the emergence of creativity in modern humans remains a mystery despite sequencing the genomes of chimpanzees and Neanderthals, our closest hominid relatives. Data-driven methods allowed us to uncover networks of genes distinguishing the three major systems of modern human personality and adaptability: emotional reactivity, self-control, and self-awareness. Now we have identified which of these genes are present in chimpanzees and Neanderthals. We replicated our findings in separate analyses of three high-coverage genomes of Neanderthals. We found that Neanderthals had nearly the same genes for emotional reactivity as chimpanzees, and they were intermediate between modern humans and chimpanzees in their numbers of genes for both self-control and self-awareness. 95% of the 267 genes we found only in modern humans were not protein-coding, including many long-non-coding RNAs in the self-awareness network. These genes may have arisen by positive selection for the characteristics of human well-being and behavioral modernity, including creativity, prosocial behavior, and healthy longevity. The genes that cluster in association with those found only in modern humans are over-expressed in brain regions involved in human self-awareness and creativity, including late-myelinating and phylogenetically recent regions of neocortex for autobiographical memory in frontal, parietal, and temporal regions, as well as related components of cortico-thalamo-ponto-cerebellar-cortical and cortico-striato-cortical loops. We conclude that modern humans have more than 200 unique non-protein-coding genes regulating co-expression of many more protein-coding genes in coordinated networks that underlie their capacities for self-awareness, creativity, prosocial behavior, and healthy longevity, which are not found in chimpanzees or Neanderthals.

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Section: Gene Co-expression In Brainmentioning

confidence: 99%

Evolution of genetic networks for human creativity

et al. 2021

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“…To obtain genes and brain regions (and their interactions) possibly associated with ATT, we attempted to balance problems in specificity/sensitivity conventionally associated with genetic and brain imaging studies by using a high p value (10 −3 ) in a GWAS, resulting in 130 genes ( Supplemental Table 1 ). Of those, 118 genes have detailed brain mRNA expression available in the human Allen Brain Atlas, 14 and according to PGL 10 are co-expressed the most in eight regions ( table 2 ). From these regions, we found that the subiculum showed higher RSFC with the habenula and the dlPFC in ATT than NAT, and that there was an interaction between the genotype of a SNP in AKAP7 (from the 130 original genes, AKAP7 was one of five that most “pointed” to the subiculum [ table 3 ]) and the subicular/dlPFC RSFC in the setting of NAT versus ATT.…”

Section: Discussionmentioning

confidence: 99%

“…Starting from a published GWAS, 13 we obtained a list of 130 genes that showed GWAS p values of 10 −3 or less (Literature box). Using the GetROIs module of PGL software (PGL box 10 ) we found 8 brain probable regions of interest. Then we used a group of psychiatric in-patients to perform brain imaging studies in ATT versus NAT in the 8 probable regions of interest [Imaging box, top].…”

Section: Discussionmentioning

confidence: 99%

“…In a newer version of PGL, we tried to mitigate this problem by using a score method that takes this into account. 10 Third, we used only RSFC as the measure for brain function. We found that the corpus callosum was highly represented in suicide-PGL, but we did not study it because it would not make much sense in RSFC.…”

Section: Discussionmentioning

confidence: 99%

“…Figure 1 shows a general pipeline, that includes the suicide-related list of genes creation, the use of PGL 10 to get the most important regions and genes associated with that phenotype, and the imaging and genetic studies that complete the whole process. Other ways of creating a list of genes associated with a phenotype or disease would work similarly.…”

Section: Methodsmentioning

confidence: 99%

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A Novel Approach to Link Genetics and Human MRI Identifies AKAP7-Dependent Subicular/Prefrontal Functional Connectivity as Altered in Suicidality

et al. 2022

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Background Brain imaging and genetics are fields acquiring data at increasing speed, but more information does not always result in a better understanding of the underlying biology. We developed the ProcessGeneLists (PGL) approach to use genetics and mRNA gene expression data to generate regions of interest for imaging studies. Methods We applied PGL to past suicide attempt (ATT): We averaged the mRNA expression levels of genes (n = 130) possibly associated with ATT (p ≤ 10−3 in a published genome-wide association study, GWAS) in each brain region studied in the Human Allen Brain Atlas (6 ex-vivo brains, 158 to 946 regions/brain have mRNA expression data) and compared that to the averaged mRNA expression levels of all other genes in each region in each brain in the atlas. Results PGL revealed 8 regions where “attempt-related genes” were differentially expressed (Wilcoxon test with Bonferroni correction 8.88−11 = <p < = 0.046). Using resting state functional connectivity (RSFC), we studied those regions in psychiatric inpatients (male/female, n = 132 with [ATT], n = 291 without [NAT] past attempt, unrelated to those in the GWAS). Among the 8 PGL-identified regions, the subiculum showed higher RSFC with habenula (p < 10−6) and dorsolateral prefrontal cortex (dlPFC pFWE < 0.05) in ATT. We genotyped one single nucleotide polymorphism (SNP) in each of the five genes (within 130 from GWAS) with most important subicular expression. AKAP7 (A-Kinase Anchoring Protein 7, important in hippocampal memory processes) showed an interaction between genotype, ATT, and subiculum/dlPFC RSFC. Conclusion PGL uncovered a brain function/genotype interaction in ATT by using published GWAS data to inform imaging studies. This could inform individualized therapies in the future.

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Gene expression networks regulated by human personality

del Val,

Díaz de la Guardia-Bolívar,

Zwir

et al. 2024

Mol Psychiatry

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Genome-wide association studies of human personality have been carried out, but transcription of the whole genome has not been studied in relation to personality in humans. We collected genome-wide expression profiles of adults to characterize the regulation of expression and function in genes related to human personality. We devised an innovative multi-omic approach to network analysis to identify the key control elements and interactions in multi-modular networks. We identified sets of transcribed genes that were co-expressed in specific brain regions with genes known to be associated with personality. Then we identified the minimum networks for the co-localized genes using bioinformatic resources. Subjects were 459 adults from the Young Finns Study who completed the Temperament and Character Inventory and provided peripheral blood for genomic and transcriptomic analysis. We identified an extrinsic network of 45 regulatory genes from seed genes in brain regions involved in self-regulation of emotional reactivity to extracellular stimuli (e.g., self-regulation of anxiety) and an intrinsic network of 43 regulatory genes from seed genes in brain regions involved in self-regulation of interpretations of meaning (e.g., production of concepts and language). We discovered that interactions between the two networks were coordinated by a control hub of 3 miRNAs and 3 protein-coding genes shared by both. Interactions of the control hub with proteins and ncRNAs identified more than 100 genes that overlap directly with known personality-related genes and more than another 4000 genes that interact indirectly. We conclude that the six-gene hub is the crux of an integrative network that orchestrates information-transfer throughout a multi-modular system of over 4000 genes enriched in liquid-liquid-phase-separation (LLPS)-related RNAs, diverse transcription factors, and hominid-specific miRNAs and lncRNAs. Gene expression networks associated with human personality regulate neuronal plasticity, epigenesis, and adaptive functioning by the interactions of salience and meaning in self-awareness.

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Process genes list: An approach to link genetics and human brain imaging

Cited by 5 publications

References 18 publications

Evolution of genetic networks for human creativity

Evolution of genetic networks for human creativity

A Novel Approach to Link Genetics and Human MRI Identifies AKAP7-Dependent Subicular/Prefrontal Functional Connectivity as Altered in Suicidality

Gene expression networks regulated by human personality

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