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Related Concept Videos

Human Genetics01:28

Human Genetics

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Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
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Depression: Overview01:18

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Depression is a prevalent mental illness marked by persistent sadness and lack of interest in previously enjoyable activities. It can take several forms, including major depression, persistent depressive disorder, and bipolar I and II disorders. Symptoms range from emotional changes like chronic worry to physical changes like sleep disturbances and suicidal thoughts. From a neurobiological perspective, depression is believed to be triggered by abnormalities in the brain's prefrontal cortex,...
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Genome-wide Association Studies-GWAS01:11

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Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
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G-protein Coupled Receptors01:21

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G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
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Antidepressant Drugs: MAOIs and Other Agents01:23

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Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
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Single Nucleotide Polymorphisms-SNPs01:05

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A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
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Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
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A Single-Nucleus Transcriptome-Wide Association Study Implicates Novel Genes in Depression Pathogenesis.

Lu Zeng1, Masashi Fujita1, Zongmei Gao1

  • 1Center for Translational and Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, New York.

Biological Psychiatry
|December 23, 2023
PubMed
Summary
This summary is machine-generated.

Researchers identified 68 candidate genes for depression, with 53 being novel, by analyzing gene expression in older adults. This study enhances understanding of depression genetics and aids in developing new treatments.

Keywords:
Depressive symptomsGenome-wide association studyMajor depressive disorderROSMAPSingle-nucleus RNA-seqTranscriptome-wide association study

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Depression is a widespread mental health issue with limited understanding of its mechanisms across life stages.
  • This lack of knowledge impedes the development of effective, novel therapeutic interventions.

Purpose of the Study:

  • To pinpoint novel candidate genes for depression treatment development.
  • To investigate the genetic underpinnings of depression using advanced molecular and statistical techniques.

Main Methods:

  • Conducted differential gene expression analysis on single-nucleus RNA sequencing data from the dorsolateral prefrontal cortex of older adults (n=424).
  • Integrated genome-wide association study (GWAS) data for depression (n=500,199) with genetic tools to analyze gene expression across 7 cell types and 52 cell subtypes.
  • Performed a transcriptome-wide association study (TWAS) for depression, followed by Mendelian randomization.

Main Results:

  • Identified 68 candidate genes associated with depression, predominantly in excitatory and inhibitory neurons; 53 of these genes are novel.
  • Demonstrated that gene expression variations in specific neuronal subtypes differentially impact depression risk.
  • Found that traits genetically correlated with depression, like neuroticism, shared more TWAS genes than less correlated traits.
  • Differential gene expression analysis highlighted specific genes (KCNN2, SCAI, WASF3, SOCS6) linked to late-life depressive symptoms in distinct neocortical cell subtypes.

Conclusions:

  • Large-scale single-nucleus RNA sequencing data effectively identifies genes altered in specific cell subtypes related to depressive symptoms.
  • These findings improve the interpretation of GWAS data, enabling prioritization of specific susceptibility genes for further research and therapeutic development.