scholarly journals Genome-Wide Significance for PCLO as a Gene for Major Depressive Disorder

2017 ◽  
Vol 20 (4) ◽  
pp. 267-270 ◽  
Author(s):  
Hamdi Mbarek ◽  
Yuri Milaneschi ◽  
Jouke-Jan Hottenga ◽  
Lannie Ligthart ◽  
Eco J. C. de Geus ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Genome Wide Association Study ◽  
Major Depressive ◽  
Significance Level ◽  
Functional Studies ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

In 2009, the first genome-wide association study (GWAS) for major depressive disorder (MDD) highlighted an association with PCLO locus on chromosome 7, although not reaching genome-wide significance level. In the present study, we revisited the original GWAS after increasing the overall sample size and the number of interrogated SNPs. In an analysis comparing 1,942 cases with lifetime diagnosis of MDD and 4,565 controls, PCLO showed a genome-wide significant association with MDD at SNP (rs2715157, p = 2.91 × 10−8) and gene-based (p = 1.48 × 10−7) level. Our results confirm the potential role of the PCLO gene in MDD, which is worth further replication and functional studies.

scholarly journals SNP and Haplotype Regional Heritability Mapping (SNHap-RHM): joint mapping of common and rare variation affecting complex traits

2021 ◽  
Author(s):  
Richard F Oppong ◽  
Pau Navarro ◽  
Chris S Haley ◽  
Sara Knott
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Complex Traits ◽  
Health Study ◽  
P Value ◽  
Major Depressive ◽  
Genome Wide ◽  
A Genome ◽  
Joint Mapping ◽  
Genomic Regions

We describe a genome-wide analytical approach, SNP and Haplotype Regional Heritability Mapping (SNHap-RHM), that provides regional estimates of the heritability across locally defined regions in the genome. This approach utilises relationship matrices that are based on sharing of SNP and haplotype alleles at local haplotype blocks delimited by recombination boundaries in the genome. We implemented the approach on simulated data and show that the haplotype-based regional GRMs capture variation that is complementary to that captured by SNP-based regional GRMs, and thus justifying the fitting of the two GRMs jointly in a single analysis (SNHap-RHM). SNHap-RHM captures regions in the genome contributing to the phenotypic variation that existing genome-wide analysis methods may fail to capture. We further demonstrate that there are real benefits to be gained from this approach by applying it to real data from about 20,000 individuals from the Generation Scotland: Scottish Family Health Study. We analysed height and major depressive disorder (MDD). We identified seven genomic regions that are genome-wide significant for height, and three regions significant at a suggestive threshold (p-value <1x10^(-5) ) for MDD. These significant regions have genes mapped to within 400kb of them. The genes mapped for height have been reported to be associated with height in humans, whiles those mapped for MDD have been reported to be associated with major depressive disorder and other psychiatry phenotypes. The results show that SNHap-RHM presents an exciting new opportunity to analyse complex traits by allowing the joint mapping of novel genomic regions tagged by either SNPs or haplotypes, potentially leading to the recovery of some of the "missing" heritability.

scholarly journals Genome-wide DNA methylation in 1-year-old infants of mothers with major depressive disorder

2016 ◽  
Vol 28 (4pt2) ◽  
pp. 1413-1419 ◽  
Author(s):  
Dante Cicchetti ◽  
Susan Hetzel ◽  
Fred A. Rogosch ◽  
Elizabeth D. Handley ◽  
Sheree L. Toth
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Low Income ◽  
Neuronal Development ◽  
Colonic Neoplasms ◽  
Major Depressive ◽  
Process Networks ◽  
Genome Wide ◽  
A Genome ◽  
Depressed Mothers

AbstractA genome-wide methylation study was conducted among a sample of 114 infants (M age = 13.2 months, SD = 1.08) of low-income urban women with (n = 73) and without (n = 41) major depressive disorder. The Illumina HumanMethylation450 BeadChip array with a GenomeStudio Methylation Module and Illumina Custom model were used to conduct differential methylation analyses. Using the 5.0 × 10–7p value, 2,119 loci were found to be significantly different between infants of depressed and nondepressed mothers. Infants of depressed mothers had greater methylation at low methylation sites (0%–29%) compared to infants of nondepressed mothers. At high levels of methylation (70%–100%), the infants of depressed mothers were predominantly hypomethylated. The mean difference in methylation between the infants of depressed and infants of nondepressed mothers was 5.23%. Disease by biomarker analyses were also conducted using GeneGo MetaCore Software. The results indicated significant cancer-related differences in biomarker networks such as prostatic neoplasms, ovarian and breast neoplasms, and colonic neoplasms. The results of a process networks analysis indicated significant differences in process networks associated with neuronal development and central nervous system functioning, as well as cardiac development between infants of depressed and nondepressed mothers. These findings indicate that early in development, infants of mothers with major depressive disorder evince epigenetic differences relative to infants of well mothers that suggest risk for later adverse health outcomes.

scholarly journals Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color

2019 ◽  
Author(s):  
Hanna Helgeland ◽  
Marte Sodeland ◽  
Nina Zoric ◽  
Jacob Seilø Torgersen ◽  
Fabian Grammes ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Beta Carotene ◽  
Color Variation ◽  
Flesh Color ◽  
Functional Studies ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Mrna And Protein Expression

AbstractRed coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL-region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, several functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.

scholarly journals Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hanna Helgeland ◽  
Marte Sodeland ◽  
Nina Zoric ◽  
Jacob Seilø Torgersen ◽  
Fabian Grammes ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Beta Carotene ◽  
Color Variation ◽  
Flesh Color ◽  
Functional Studies ◽  
Genetic Components ◽  
Genome Wide ◽  
A Genome ◽  
Mrna And Protein Expression

AbstractRed coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL- region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.

scholarly journals SNP and Haplotype Regional Heritability Mapping (SNHap-RHM): Joint Mapping of Common and Rare Variation Affecting Complex Traits

2022 ◽  
Vol 12 ◽  
Author(s):  
Richard F. Oppong ◽  
Thibaud Boutin ◽  
Archie Campbell ◽  
Andrew M. McIntosh ◽  
David Porteous ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Complex Traits ◽  
Simulated Data ◽  
Health Study ◽  
Major Depressive ◽  
Genome Wide ◽  
A Genome ◽  
Joint Mapping ◽  
Genomic Regions

We describe a genome-wide analytical approach, SNP and Haplotype Regional Heritability Mapping (SNHap-RHM), that provides regional estimates of the heritability across locally defined regions in the genome. This approach utilises relationship matrices that are based on sharing of SNP and haplotype alleles at local haplotype blocks delimited by recombination boundaries in the genome. We implemented the approach on simulated data and show that the haplotype-based regional GRMs capture variation that is complementary to that captured by SNP-based regional GRMs, and thus justifying the fitting of the two GRMs jointly in a single analysis (SNHap-RHM). SNHap-RHM captures regions in the genome contributing to the phenotypic variation that existing genome-wide analysis methods may fail to capture. We further demonstrate that there are real benefits to be gained from this approach by applying it to real data from about 20,000 individuals from the Generation Scotland: Scottish Family Health Study. We analysed height and major depressive disorder (MDD). We identified seven genomic regions that are genome-wide significant for height, and three regions significant at a suggestive threshold (p-value &lt; 1 × 10−5) for MDD. These significant regions have genes mapped to within 400 kb of them. The genes mapped for height have been reported to be associated with height in humans. Similarly, those mapped for MDD have been reported to be associated with major depressive disorder and other psychiatry phenotypes. The results show that SNHap-RHM presents an exciting new opportunity to analyse complex traits by allowing the joint mapping of novel genomic regions tagged by either SNPs or haplotypes, potentially leading to the recovery of some of the “missing” heritability.

scholarly journals Using genetic drug-target networks to develop new drug hypotheses for major depressive disorder

2018 ◽  
Author(s):  
Héléna A Gaspar ◽  
Zachary Gerring ◽  
Christopher Hübel ◽  
Christel M Middeldorp ◽  
Eske M Derks ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Drug Target ◽  
Model Systems ◽  
Genome Wide Association ◽  
Multiple Testing Correction ◽  
Major Depressive ◽  
Expression Levels ◽  
Genome Wide ◽  
A Genome

AbstractThe major depressive disorder (MDD) working group of the Psychiatric Genomics Consortium (PGC) has published a genome-wide association study (GWAS) for MDD in 130,664 cases, identifying 44 risk variants. We used these results to investigate potential drug targets and repurposing opportunities. We built easily interpretable bipartite drug-target networks integrating interactions between drugs and their targets, genome-wide association statistics and genetically predicted expression levels in different tissues, using our online tool Drug Targetor (drugtargetor.com). We also investigated drug-target relationships and drug effects on gene expression that could be impacting MDD. MAGMA was used to perform pathway analyses and S-PrediXcan to investigate the directionality of tissue-specific expression levels in patients vs. controls. Outside the major histocompatibility complex (MHC) region, 25 druggable genes were significantly associated with MDD after multiple testing correction, and 19 were suggestively significant. Several drug classes were significantly enriched, including monoamine reuptake inhibitors, sex hormones, antipsychotics and antihistamines, indicating an effect on MDD and potential repurposing opportunities. These findings require validation in model systems and clinical examination, but also show that GWAS may become a rich source of new therapeutic hypotheses for MDD and other psychiatric disorders that need new – and better – treatment options.

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