Related Experiment Video
Updated: May 12, 2026
08:27
Large-Scale Multi-Omics Genome-Wide Association Studies (Mo-GWAS): Guidelines for Sample Preparation and Normalization
Published on: July 27, 2021
The impact of improved microarray coverage and larger sample sizes on future genome-wide association studies
Karla J Lindquist1, Eric Jorgenson, Thomas J Hoffmann
1Department of Epidemiology and Biostatistics, University of California, San Francisco, CA 94158-9001, USA.
Genetic Epidemiology
|March 27, 2013
Summary
Future genome-wide association studies (GWAS) can detect more genetic associations for chronic diseases. Increasing sample size, rather than SNP array coverage, is key to uncovering additional heritability for complex traits.
Area of Science:
- Genetics
- Genomics
- Human Disease Research
Background:
- Genome-wide association studies (GWAS) have identified numerous single nucleotide polymorphisms (SNPs) linked to complex traits.
- A significant portion of the genetic heritability for most complex traits remains unexplained by current GWAS findings.
Purpose of the Study:
- To evaluate the potential of future GWAS to identify novel SNP associations and explain additional heritability.
- To assess the impact of enhanced SNP array coverage, imputation techniques, and reduced genotyping costs on future discoveries.
Main Methods:
- Assessed pairwise and imputation coverage of all human genome SNPs using commercially available GWAS arrays and the 1000 Genomes Project.
- Analyzed 6 years of GWAS data for 172 chronic diseases, calculating detection power considering array coverage and sample size.
- Modeled detection power under various scenarios of improved coverage and/or sample sizes.
Main Results:
- Estimated that less than one-fifth of all GWAS-detectable SNPs for chronic diseases have been identified by previous GWAS.
- Demonstrated that increasing sample size significantly enhances the potential for future GWAS to detect additional SNP-disease associations.
- Found that sample size expansion has a greater impact on uncovering heritability than increasing SNP array coverage.
Conclusions:
- Future GWAS hold substantial potential for identifying previously undetected SNP associations and explaining more heritability in chronic diseases.
- Prioritizing sample size augmentation in GWAS design is crucial for maximizing the discovery of genetic underpinnings of complex traits.
- Technological advancements in genotyping and imputation improve but are secondary to sample size in driving future genetic discoveries.
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...
02:34DNA Microarrays
Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...
03:00Next-generation Sequencing
The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features.
02:02Genomics
Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
03:21Genome Size and the Evolution of New Genes
While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.
03:21Genome Size and the Evolution of New Genes
While every living organism has a genome of some kind (be it RNA, or DNA), there is considerable variation in the sizes of these blueprints. One major factor that impacts genome size is whether the organism is prokaryotic or eukaryotic. In prokaryotes, the genome contains little to no non-coding sequence, such that genes are tightly clustered in groups or operons sequentially along the chromosome. Conversely, the genes in eukaryotes are punctuated by long stretches of non-coding sequence.