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Updated: Jun 10, 2026
05:51
A Strategy to Identify de Novo Mutations in Common Disorders such as Autism and Schizophrenia
Published on: June 15, 2011
A genome-wide scan for common alleles affecting risk for autism
Richard Anney1, Lambertus Klei, Dalila Pinto
1Department of Psychiatry, School of Medicine, Trinity College, Dublin 8, Ireland.
Human Molecular Genetics
|July 29, 2010
Summary
Researchers investigated common genetic variations linked to autism spectrum disorder (ASD). While a specific marker (rs4141463) in MACROD2 showed initial promise, its association strength diminished in replication studies, highlighting the complexity of ASD genetics.
Area of Science:
- Genetics
- Neuroscience
- Pediatrics
Background:
- Autism spectrum disorders (ASDs) have a significant genetic component, but most identified risks stem from rare variants like copy number variants (CNVs).
- Identifying common genetic variations contributing to ASD risk is crucial for understanding its etiology.
Purpose of the Study:
- To identify common genetic risk variations for autism spectrum disorders (ASDs).
- To analyze single-nucleotide polymorphisms (SNPs) for association with ASD in a large cohort of families.
Main Methods:
- Genotyped 1,558 ASD families using 1 million single-nucleotide polymorphisms (SNPs).
- Conducted genome-wide association analyses to identify SNPs associated with ASD.
- Performed replication analyses on a smaller sample to validate initial findings.
Main Results:
- The marker rs4141463 within the MACROD2 gene initially crossed the genome-wide significance threshold (P < 5 × 10⁻⁸).
- Replication analysis showed a reduced effect size for rs4141463, consistent with the winner's curse phenomenon.
- Combined analyses for rs4141463 narrowly missed the genome-wide significance threshold.
- Exploratory analyses identified potential associations with genes KIAA0564, PLD5, POU6F2, ST8SIA2, and TAF1C, though not significant after multiple testing correction.
Conclusions:
- Common variants, such as rs4141463, may play a role in ASD susceptibility, but their effect sizes can be overestimated in initial discovery cohorts.
- Further research is needed to confirm the role of common variants and identify additional genes contributing to ASD risk.
- The study underscores the complexity of the genetic architecture of autism spectrum disorders.
Related Concept Videos
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...
01:19Autism Spectrum Disorder
Autism spectrum disorder (ASD) is a neurodevelopmental condition marked by persistent deficits in social communication and interaction alongside restrictive and repetitive behaviors or interests. ASD is sometimes accompanied by intellectual impairment.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
02:46Genetic Screens
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
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,...
01:23Behavioral 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...
02:26Comparing Copy Number Variations and SNPs
Sequencing of the human genome has opened up several best-kept secrets of the genome. Scientists have identified thousands of genome variations that exist within a population. These variations can be a single nucleotide or a larger chromosomal variation.
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...
Copy number variations or CNVs are the structural variations that cover more than 1kb of DNA sequence. The single nucleotide polymorphism (SNP), on the other hand, is a single nucleotide change or a point mutation that is found in more than 1%...