Podcast
Questions and Answers
What is the purpose of Genome-wide association (GWA) studies?
What is the purpose of Genome-wide association (GWA) studies?
To genotype thousands of DNA variants across the genome to identify associations with traits of interest.
Explain the concept of polygenic scores.
Explain the concept of polygenic scores.
Polygenic scores are weighted sums of SNP genotypes, with weights derived from GWA summary statistics.
How do GCTA and LD score regression contribute to genetic research?
How do GCTA and LD score regression contribute to genetic research?
They are methods for estimating heritability and genetic correlations using GWA summary statistics.
What do multivariate GWA studies reveal about psychiatric disorders?
What do multivariate GWA studies reveal about psychiatric disorders?
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How do polygenic scores help in predicting risk for complex traits?
How do polygenic scores help in predicting risk for complex traits?
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What is the significance of the genetic architecture of psychopathology revealed by GCTA and LD score regression?
What is the significance of the genetic architecture of psychopathology revealed by GCTA and LD score regression?
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What percentage of the variance in height can be explained by 180 SNPs?
What percentage of the variance in height can be explained by 180 SNPs?
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How much of the variance in total years of education can be explained using 3,500 SNPs?
How much of the variance in total years of education can be explained using 3,500 SNPs?
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What percentage of the variance in childhood IQ can be explained by 180 SNPs?
What percentage of the variance in childhood IQ can be explained by 180 SNPs?
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How much of the total variance of liability for coronary artery disease is accounted for by 150 SNPs?
How much of the total variance of liability for coronary artery disease is accounted for by 150 SNPs?
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What is the biggest question in genomic sciences related to GWA studies?
What is the biggest question in genomic sciences related to GWA studies?
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What may be responsible for some of the missing heritability beyond common SNPs?
What may be responsible for some of the missing heritability beyond common SNPs?
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What is pleiotropy?
What is pleiotropy?
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Explain how pleiotropy might drive polygenicity.
Explain how pleiotropy might drive polygenicity.
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What is the significance of the plummeting cost of whole-genome sequencing?
What is the significance of the plummeting cost of whole-genome sequencing?
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What did GWA studies confirm about the genetic overlap between schizophrenia and bipolar disorder?
What did GWA studies confirm about the genetic overlap between schizophrenia and bipolar disorder?
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What did a multivariate GWA analysis of five major psychiatric disorders find?
What did a multivariate GWA analysis of five major psychiatric disorders find?
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How does a more truly multivariate GWA analysis differ from a traditional analysis?
How does a more truly multivariate GWA analysis differ from a traditional analysis?
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Study Notes
Genome-Wide Association (GWA) Studies
- GWA studies genotype thousands of DNA variants across the genome to identify associations with traits of interest.
- GWA studies have revealed that complex traits are extremely polygenic, with thousands of SNPs contributing to heritability.
Polygenic Scores
- Polygenic scores are weighted sums of SNP genotypes, with weights derived from GWA summary statistics.
- Polygenic scores can be used to predict risk for complex traits, even when individual SNPs have small effects.
Genetic Architecture of Psychopathology
- GCTA and LD score regression have revealed substantial genetic correlations between different psychiatric disorders, suggesting that they share a common genetic architecture.
- Future research will focus on identifying the specific genes and pathways that contribute to this shared genetic architecture.
Causal Modelling of Gene-Environment Interplay
- Gene-environment interactions are complex and difficult to study using traditional methods.
- Future research will use polygenic scores and other tools from behavioral genomics to develop causal models of gene-environment interplay.
Future of GWA Studies
- The plummeting cost of whole-genome sequencing approaches the cost of DNA arrays.
- Larger samples will be amassed, and the common SNPs on current DNA arrays will account for more of the missing heritability.
Pleiotropy and Polygenicity
- Pleiotropy is the manifold effects of genes, where each gene affects many traits.
- Pleiotropy might drive polygenicity, as many traits are influenced by many genes.
- Substantial pleiotropy has been found for cognitive and learning abilities and disabilities, childhood psychopathology, and adult psychosis.
Multivariate GWA Studies
- Multivariate GWA studies focus on genetic associations in common across traits.
- A multivariate GWA analysis of five major psychiatric disorders found three SNPs that were associated with all five disorders.
Implications for Developmental Research
- Pleiotropic polygenic scores could be created that predict what is in common across broad domains such as psychopathology and cognitive abilities and disabilities.
Implications for Different Traits
- For height, 180 SNPs account for 10% of the variance, which increases to 13% when more SNPs are added.
- For total years of education, GWA meta-analysis with more than 100,000 individuals explained about 1% of the variance using 3,500 SNPs and 2.5% of the variance using all 2.5 million SNPs.
- For childhood IQ, 180 SNPs explained about 1% of the variance.
- For medical disorders, specific SNPs in total account for up to about 8% of the liability.
- For coronary artery disease, 150 SNPs accounted for about 5% of the total variance of liability.
- For schizophrenia, significant SNPs accounted for about 1% of the liability, and all SNPs accounted for almost 6% of the liability.
- For bipolar disorder, SNPs account for 1% to 3% of the liability.
Beyond Common SNPs on Current DNA Arrays
- Less common DNA variants, including less common SNPs, may be responsible for some of the missing heritability.
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Description
Explore the concept of Genome-Wide Association (GWA) studies and how they have revolutionized the understanding of complex traits influenced by multiple genes. Learn about the methods like GCTA and LD score regression used to estimate heritability.