Related Experiment Video
Updated: Jul 2, 2026
05:51
A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism
Edwin J C G van den Oord1, Po-Hsiu Kuo, Annette M Hartmann
1Center for Biomarker Research and Personalized Medicine, Medical College of Virginia, Virginia Commonwealth University, PO Box 980533, Richmond, VA 23298-0533, USA. ejvandenoord@vcu.edu
Archives of General Psychiatry
|September 3, 2008
Summary
This study identified genetic markers in the MAMDC1 gene associated with neuroticism. While small, these findings highlight the potential of genome-wide association studies for discovering new pathways in psychiatric disorders.
Area of Science:
- Psychiatric Genetics
- Behavioral Genetics
- Molecular Psychiatry
Background:
- Neuroticism, a tendency toward negative affect, is linked to internalizing disorders like anxiety and depression.
- Neuroticism significantly contributes to the comorbidity observed between these psychiatric conditions.
Purpose of the Study:
- To identify common genetic variants influencing neuroticism.
- To advance understanding of psychiatric disorder comorbidity.
- To inform the development of novel therapeutic strategies.
Main Methods:
- A genome-wide association study (GWAS) analyzed over 420,000 genetic markers in 1227 US individuals.
- Promising markers underwent replication in a German sample of 1880 individuals.
- A stringent replication definition and significance threshold were employed to minimize false positives.
Main Results:
- Single-nucleotide polymorphisms (SNPs) within the MAMDC1 gene showed the most promising association with neuroticism.
- These SNPs demonstrated consistent effects and directionality across both GWAS and replication samples.
- Combined analyses revealed several significant SNPs, meeting the study's threshold for potential pathogenic relevance.
Conclusions:
- The identified MAMDC1 SNPs have small effect sizes, potentially limiting immediate clinical utility.
- This GWAS demonstrates the power of large-scale genetic studies to uncover novel pathogenic pathways.
- Future research may leverage these pathways to develop more potent biomarkers for psychiatric conditions.
Related Concept Videos
01:28Human Genetics
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...
The complex relationship between genetics and psychology is observable through common biological components such...
01:11Genome-wide Association Studies-GWAS
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.
GWAS does not require the identification of the target gene involved in...
GWAS does not require the identification of the target gene involved in...
01:23Behavioral Genetics and Its Designs
Behavior genetics explores how genetic inheritance influences human behavior. It focuses on how genes, passed from parents to offspring, contribute to the development of behavioral traits and tendencies. This branch of genetics seeks to understand the complex interplay between inherited genetic factors and environmental influences in shaping our behaviors.
The primary methodologies used in behavior genetics include family studies, twin studies, and adoption studies, each providing unique...
The primary methodologies used in behavior genetics include family studies, twin studies, and adoption studies, each providing unique...
01:05Single Nucleotide Polymorphisms-SNPs
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,...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...