Genome-wide association testing beyond SNPs
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Decades of genetic association testing in human cohorts have provided important insights into the genetic architecture and biological underpinnings of complex traits and diseases. However, for certain traits, genome-wide association studies (GWAS) for common SNPs are approaching signal saturation, which underscores the need to explore other types of genetic variation to understand the genetic basis of traits and diseases. Copy number variation (CNV) is an important source of heritability that is well known to functionally affect human traits. Recent technological and computational advances enable the large-scale, genome-wide evaluation of CNVs, with implications for downstream applications such as polygenic risk scoring and drug target identification. Here, we review the current state of CNV-GWAS, discuss current limitations in resource infrastructure that need to be overcome to enable the wider uptake of CNV-GWAS results, highlight emerging opportunities and suggest guidelines and standards for future GWAS for genetic variation beyond SNPs at scale.
Date Issued
2025-03-01
Date Acceptance
2024-09-03
Citation
Nature Reviews Genetics, 2025, 26 (3), pp.156-170
ISSN
1471-0056
Publisher
Nature Research
Start Page
156
End Page
170
Journal / Book Title
Nature Reviews Genetics
Volume
26
Issue
3
Copyright Statement
Copyright © 2025 Springer Nature. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39375560
PII: 10.1038/s41576-024-00778-y
Subjects
CNVS
COMMON DISEASES
COPY-NUMBER VARIATION
Genetics & Heredity
HERITABILITY
INFERENCE
Life Sciences & Biomedicine
POLYMORPHISM
REVOLUTION
Science & Technology
STANDARDS
STRUCTURAL VARIATION
VARIANTS
Publication Status
Accepted
Coverage Spatial
England
Date Publish Online
2024-10-07