Molecular neuroanatomy of anorexia nervosa

AbstractAnorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using unbiased genome-wide methods, recent studies have associated a variety of genes with the disorder. We characterized these genes by projecting them into aggregated gene expression data from reference transcriptomic atlases of the prenatal and adult human brain. We found that genes from an induced stem cell study of anorexia nervosa are expressed at higher levels in the lateral parabrachial and the ventral tegmental areas. The adult expression enrichment of the lateral parabrachial is confirmed with genes from two independent genetic studies. In the fetal brain, enrichment of the ventral tegmental area is also observed for the six genes near the only common variant associated with the disorder (rs4622308). We also observed signals in the adult and fetal pontine raphe, but they were not observed when using the genes from the genetic studies. In addition to signals related to calcitonin gene-related peptide neurons and the tachykinin, we found more than the expected number of microglia marker genes within the gene sets. Using mouse transcriptomic data, we identified several anorexia nervosa associated genes that are differentially expressed during food deprivation. While these genes that respond to fasting are not enriched in the gene sets, we highlightRPS26which is proximal to rs4622308. We did not observe expression enrichment in the cingulate cortex or hypothalamus suggesting other targets for deep brain stimulation should be considered for severe cases. This work improves our understanding of the neurobiological causes of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.

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Faculty Opinions recommendation of Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.727349473.793546331 ◽

2018 ◽

Author(s):

Luc Mallet

Keyword(s):

Anorexia Nervosa ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Open Label ◽

Open Label Trial ◽

Treatment Refractory ◽

Deep Brain ◽

Stimulation Of

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The mutL Gene as a Genome-Wide Taxonomic Marker for High Resolution Discrimination of Lactiplantibacillus plantarum and Its Closely Related Taxa

Microorganisms ◽

10.3390/microorganisms9081570 ◽

2021 ◽

Vol 9 (8) ◽

pp. 1570

Author(s):

Chien-Hsun Huang ◽

Chih-Chieh Chen ◽

Yu-Chun Lin ◽

Chia-Hsuan Chen ◽

Ai-Yun Lee ◽

...

Keyword(s):

16S Rrna ◽

16S Rrna Gene ◽

Target Genes ◽

Marker Genes ◽

Rrna Gene ◽

Accurate Identification ◽

Discrimination Power ◽

Sequence Identity ◽

Genome Wide ◽

A Genome

The current taxonomy of the Lactiplantibacillus plantarum group comprises of 17 closely related species that are indistinguishable from each other by using commonly used 16S rRNA gene sequencing. In this study, a whole-genome-based analysis was carried out for exploring the highly distinguished target genes whose interspecific sequence identity is significantly less than those of 16S rRNA or conventional housekeeping genes. In silico analyses of 774 core genes by the cano-wgMLST_BacCompare analytics platform indicated that csbB, morA, murI, mutL, ntpJ, rutB, trmK, ydaF, and yhhX genes were the most promising candidates. Subsequently, the mutL gene was selected, and the discrimination power was further evaluated using Sanger sequencing. Among the type strains, mutL exhibited a clearly superior sequence identity (61.6–85.6%; average: 66.6%) to the 16S rRNA gene (96.7–100%; average: 98.4%) and the conventional phylogenetic marker genes (e.g., dnaJ, dnaK, pheS, recA, and rpoA), respectively, which could be used to separat tested strains into various species clusters. Consequently, species-specific primers were developed for fast and accurate identification of L. pentosus, L. argentoratensis, L. plantarum, and L. paraplantarum. During this study, one strain (BCRC 06B0048, L. pentosus) exhibited not only relatively low mutL sequence identities (97.0%) but also a low digital DNA–DNA hybridization value (78.1%) with the type strain DSM 20314T, signifying that it exhibits potential for reclassification as a novel subspecies. Our data demonstrate that mutL can be a genome-wide target for identifying and classifying the L. plantarum group species and for differentiating novel taxa from known species.

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New resources for genetic studies in maize ( Zea mays L.): a genome‐wide Maize6H‐60K single nucleotide polymorphism array and its application

The Plant Journal ◽

10.1111/tpj.15089 ◽

2020 ◽

Author(s):

Hongli Tian ◽

Yang Yang ◽

Hongmei Yi ◽

Liwen Xu ◽

Hang He ◽

...

Keyword(s):

Single Nucleotide Polymorphism ◽

Zea Mays ◽

Zea Mays L ◽

Single Nucleotide Polymorphism Array ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Genetic Studies ◽

Genome Wide ◽

A Genome

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Importance of Adult Dmbx1 in Long-Lasting Orexigenic Effect of Agouti-Related Peptide

Endocrinology ◽

10.1210/en.2015-1560 ◽

2016 ◽

Vol 157 (1) ◽

pp. 245-257 ◽

Cited By ~ 1

Author(s):

Seiichiro Hirono ◽

Eun Young Lee ◽

Shunsuke Kuribayashi ◽

Takahiro Fukuda ◽

Naokatsu Saeki ◽

...

Keyword(s):

Mouse Strain ◽

Energy Homeostasis ◽

Expression Patterns ◽

Critical Role ◽

Fetal Brain ◽

Cre Recombinase ◽

Calcitonin Gene Related Peptide ◽

Adult Brain ◽

Related Peptide ◽

Calcitonin Gene

Abstract Dmbx1 is a brain-specific homeodomain transcription factor expressed primarily during embryogenesis, and its systemic disruption (Dmbx1−/−) in the ICR mouse strain resulted in leanness associated with impaired long-lasting orexigenic effect of agouti-related peptide (AgRP). Because spatial and temporal expression patterns of Dmbx1 change dramatically during embryogenesis, it remains unknown when and where Dmbx1 plays a critical role in energy homeostasis. In the present study, the physiological roles of Dmbx1 were examined by its conditional disruption (Dmbx1loxP/loxP) in the C57BL/6 mouse strain. Although Dmbx1 disruption in fetal brain resulted in neonatal lethality, its disruption by synapsin promoter-driven Cre recombinase, which eliminated Dmbx1 expression postnatally, exempted the mice (Syn-Cre;Dmbx1loxP/loxP mice) from lethality. Syn-Cre;Dmbx1loxP/loxP mice show mild leanness and impaired long-lasting orexigenic action of AgRP, demonstrating the physiological relevance of Dmbx1 in the adult. Visualization of Dmbx1-expressing neurons in adult brain using the mice harboring tamoxifen-inducible Cre recombinase in the Dmbx1 locus (Dmbx1CreERT2/+ mice) revealed Dmbx1 expression in small numbers of neurons in restricted regions, including the lateral parabrachial nucleus (LPB). Notably, c-Fos expression in LPB was increased at 48 hours after AgRP administration in Dmbx1loxP/loxP mice but not in Syn-Cre;Dmbx1loxP/loxP mice. These c-Fos-positive neurons in LPB did not coincide with neurons expressing Dmbx1 or melanocortin 4 receptor but did coincide with those expressing calcitonin gene-related peptide. Accordingly, Dmbx1 in the adult LPB is required for the long-lasting orexigenic effect of AgRP via the neural circuitry involving calcitonin gene-related peptide neurons.

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Detecting Genetic Associations betweenATG5and Lupus Nephritis bytrans-eQTL

Journal of Immunology Research ◽

10.1155/2015/153132 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Yue-miao Zhang ◽

Fa-juan Cheng ◽

Xu-jie Zhou ◽

Yuan-yuan Qi ◽

Ping Hou ◽

...

Keyword(s):

Lupus Nephritis ◽

Lupus Erythematosus ◽

Clinical Information ◽

Nucleotide Polymorphisms ◽

Genetic Associations ◽

Single Nucleotide ◽

Genetic Studies ◽

Genome Wide ◽

Custom Made ◽

Regulatory Effects

Objectives. Numerous loci were identified to perturb gene expression intrans. As elevatedATG5expression was observed in systemic lupus erythematosus (SLE), the study was conducted to analyze the genome-wide genetic regulatory mechanisms associated withATG5expression in a Chinese population with lupus nephritis (LN).Methods. The online expression quantitative trait loci database was searched fortrans-expression single nucleotide polymorphisms (trans-eSNPs) ofATG5. Taggingtrans-eSNPs were genotyped by a custom-made genotyping chip in 280 patients and 199 controls. For positive findings, clinical information and bioinformation analyses were performed.Results. Fourtrans-eSNPs were observed to be associated with susceptibility to LN (P< 0.05), including ANKRD50 rs17008504, AGA rs2271100, PAK7 rs6056923, and TET2 rs1391441, while seven othertrans-eSNPs showed marginal significant associations (0.05 <P< 0.1). Correlations between thetrans-eSNPs andATG5expression and different expression levels ofATG5in SLE patients and controls were validated, and their regulatory effects were annotated. However, no significant associations were observed between different genotypes oftrans-eSNPs and severity or outcome of the patients.Conclusion. Using the new systemic genetics approach, we identified 10 loci associated with susceptibility to LN potentially, which may be complementary to future pathway based genetic studies.

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Moving into a new era of periodontal genetic studies: relevance of large case-control samples using severe phenotypes for genome-wide association studies

Journal of Periodontal Research ◽

10.1111/jre.12167 ◽

2014 ◽

Vol 49 (6) ◽

pp. 683-695 ◽

Cited By ~ 33

Author(s):

R. D. Vaithilingam ◽

S. H. Safii ◽

N. A. Baharuddin ◽

C. C. Ng ◽

S. C. Cheong ◽

...

Keyword(s):

Association Studies ◽

Case Control ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genetic Studies ◽

New Era ◽

Genome Wide ◽

Large Case ◽

Control Samples

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Impact of depression and stress on placental DNA methylation in ethnically diverse pregnant women

Epigenomics ◽

10.2217/epi-2021-0192 ◽

2021 ◽

Author(s):

Markos Tesfaye ◽

Suvo Chatterjee ◽

Xuehuo Zeng ◽

Paule Joseph ◽

Fasil Tekola-Ayele

Keyword(s):

Dna Methylation ◽

Fetal Brain ◽

Ethnically Diverse ◽

Antenatal Depression ◽

Epigenetic Changes ◽

Clinical Trial Registration ◽

False Discovery ◽

Genome Wide ◽

Neuropsychiatric Diseases ◽

Registration Number

Aim: To investigate the association between placental genome-wide methylation at birth and antenatal depression and stress during pregnancy. Methods: We examined the association between placental genome-wide DNA methylation (n = 301) and maternal depression and stress assessed at six gestation periods during pregnancy. Correlation between DNA methylation at the significantly associated CpGs and expression of nearby genes in the placenta was tested. Results: Depression and stress were associated with methylation of 16 CpGs and two CpGs, respectively, at a 5% false discovery rate. Methylation levels at two of the CpGs associated with depression were significantly associated with expression of ADAM23 and CTDP1, genes implicated in neurodevelopment and neuropsychiatric diseases. Conclusion: Placental epigenetic changes linked to antenatal depression suggest potential fetal brain programming. Clinical trial registration number: NCT00912132 (ClinicalTrials.gov)

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Genome-wide association study of treatment-resistance in depression and meta-analysis of three independent samples

The British Journal of Psychiatry ◽

10.1192/bjp.2018.256 ◽

2018 ◽

Vol 214 (1) ◽

pp. 36-41 ◽

Cited By ~ 13

Author(s):

Chiara Fabbri ◽

Siegfried Kasper ◽

Alexander Kautzky ◽

Lucie Bartova ◽

Markus Dold ◽

...

Keyword(s):

Genome Wide Association Study ◽

Meta Analysis ◽

Adenosine Monophosphate ◽

Research Support ◽

Antidepressant Treatments ◽

Advisory Boards ◽

Gene Sets ◽

Genome Wide ◽

A Genome ◽

Resistant Depression

BackgroundTreatment-resistant depression (TRD) is the most problematic outcome of depression in terms of functional impairment, suicidal thoughts and decline in physical health.AimsTo investigate the genetic predictors of TRD using a genome-wide approach to contribute to the development of precision medicine.MethodA sample recruited by the European Group for the Study of Resistant Depression (GSRD) including 1148 patients with major depressive disorder (MDD) was characterised for the occurrence of TRD (lack of response to at least two adequate antidepressant treatments) and genotyped using the Infinium PsychArray. Three clinically relevant patient groups were considered: TRD, responders and non-responders to the first antidepressant trial, thus outcomes were based on comparisons of these groups. Genetic analyses were performed at the variant, gene and gene-set (i.e. functionally related genes) level. Additive regression models of the outcomes and relevant covariates were used in the GSRD participants and in a fixed-effect meta-analysis performed between GSRD, STAR*D (n = 1316) and GENDEP (n = 761) participants.ResultsNo individual polymorphism or gene was associated with TRD, although some suggestive signals showed enrichment in cytoskeleton regulation, transcription modulation and calcium signalling. Two gene sets (GO:0043949 and GO:0000183) were associated with TRD versus response and TRD versus response and non-response to the first treatment in the GSRD participants and in the meta-analysis, respectively (corrected P = 0.030 and P = 0.027).ConclusionsThe identified gene sets are involved in cyclic adenosine monophosphate mediated signal and chromatin silencing, two processes previously implicated in antidepressant action. They represent possible biomarkers to implement personalised antidepressant treatments and targets for new antidepressants.Declaration of interestD.S. has received grant/research support from GlaxoSmithKline and Lundbeck; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen and Lundbeck. S.M. has been a consultant or served on advisory boards for: AstraZeneca, Bristol-Myers Squibb, Forest, Johnson & Johnson, Leo, Lundbeck, Medelink, Neurim, Pierre Fabre, Richter. S.K. has received grant/research support from Eli Lilly, Lundbeck, Bristol-Myers Squibb, GlaxoSmithKline, Organon, Sepracor and Servier; has served as a consultant or on advisory boards for AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly, Lundbeck, Pfizer, Organon, Schwabe, Sepracor, Servier, Janssen and Novartis; and has served on speakers' bureaus for AstraZeneca, Eli Lily, Lundbeck, Schwabe, Sepracor, Servier, Pierre Fabre, Janssen and Neuraxpharm. J.Z. has received grant/research support from Lundbeck, Servier, Brainsway and Pfizer, has served as a consultant or on advisory boards for Servier, Pfizer, Abbott, Lilly, Actelion, AstraZeneca and Roche and has served on speakers' bureaus for Lundbeck, Roch, Lilly, Servier, Pfizer and Abbott. J.M. is a member of the Board of the Lundbeck International Neuroscience Foundation and of Advisory Board of Servier. A.S. is or has been consultant/speaker for: Abbott, AbbVie, Angelini, Astra Zeneca, Clinical Data, Boehringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi and Servier. C.M.L. receives research support from RGA UK Services Limited.

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