Benefits and limitations of genome-wide association studies

Vivian Tam; Nikunj Patel; Michelle Turcotte; Yohan Bossé; Guillaume Paré; David Meyre

doi:10.1038/s41576-019-0127-1

Abstract

Genome-wide association studies (GWAS) involve testing genetic variants across the genomes of many individuals to identify genotype-phenotype associations. GWAS have revolutionized the field of complex disease genetics over the past decade, providing numerous compelling associations for human complex traits and diseases. Despite clear successes in identifying novel disease susceptibility genes and biological pathways and in translating these findings into clinical care, GWAS have not been without controversy. Prominent criticisms include concerns that GWAS will eventually implicate the entire genome in disease predisposition and that most association signals reflect variants and genes with no direct biological relevance to disease. In this Review, we comprehensively assess the benefits and limitations of GWAS in human populations and discuss the relevance of performing more GWAS.

Keywords

Genome-wide association studyBiologyGenetic associationDiseaseGeneticsComputational biologyGenomeSingle-nucleotide polymorphismGenotypeGeneMedicinePathology

MeSH Terms

AnimalsGenetic Association StudiesGenetic Predisposition to DiseaseGenetic VariationGenomeGenome-Wide Association StudyGenotypeHumansPhenotype

Affiliated Institutions

Related Publications

Prioritizing candidate disease genes by network-based boosting of genome-wide association data

Insuk Lee , U. Martin Blom , Peggy I. Wang +2 more

Network “guilt by association” (GBA) is a proven approach for identifying novel disease genes based on the observation that similar mutational phenotypes arise from functionally...

2011 Genome Research 704 citations

Liver and Adipose Expression Associated SNPs Are Enriched for Association to Type 2 Diabetes

Hua Zhong , John Beaulaurier , Pek Yee Lum +19 more

Genome-wide association studies (GWAS) have demonstrated the ability to identify the strongest causal common variants in complex human diseases. However, to date, the massive da...

2010 PLoS Genetics 172 citations

Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

Anubha Mahajan , Daniel Taliun , Matthias Thurner +96 more

We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. W...

2018 Nature Genetics 1834 citations

Fine Mapping of Five Loci Associated with Low-Density Lipoprotein Cholesterol Detects Variants That Double the Explained Heritability

Serena Sanna , Bingshan Li , Antonella Mulas +22 more

Complex trait genome-wide association studies (GWAS) provide an efficient strategy for evaluating large numbers of common variants in large numbers of individuals and for identi...

2011 PLoS Genetics 172 citations

Genomic inflation factors under polygenic inheritance

Jian Yang , Michael N. Weedon , Shaun Purcell +18 more

Population structure, including population stratification and cryptic relatedness, can cause spurious associations in genome-wide association studies (GWAS). Usually, the scaled...

2011 European Journal of Human Genetics 607 citations

Publication Info

Year: 2019
Type: review
Volume: 20
Issue: 8
Pages: 467-484
Citations: 2028
Access: Closed

External Links

Download PDF (Free) View on DOI.org PubMed Semantic Scholar

Social Impact

Altmetric

Benefits and limitations of genome-wide association studies

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

2028

OpenAlex

Influential

Cite This

APA Style

                            
                                
                                    Vivian Tam, 
                                
                                    Nikunj Patel, 
                                
                                    Michelle Turcotte
                                
                                et al.
                            
                            (2019). 
                            Benefits and limitations of genome-wide association studies. 
                            Nature Reviews Genetics
                            , 20
                            (8)
                            , 467-484.
                            https://doi.org/10.1038/s41576-019-0127-1
                        

Identifiers

DOI: 10.1038/s41576-019-0127-1
PMID: 31068683

Data Quality

Data completeness: 81%