Related Experiment Video
Updated: May 21, 2026
04:41
Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
Published on: January 9, 2020
Genome-wide associations of structural variants with human traits through imputation from long-read assemblies
Wei-Yang Bai1,2, Shuli Liu1,2, Zhongqu Duan1,2
1New Cornerstone Science Laboratory, School of Life Sciences, Westlake University, Hangzhou, China.
Nature Genetics
|May 19, 2026
Summary
Structural variants (SVs) significantly impact human traits, but are hard to study. This research developed a tool to impute SVs from common genetic data, revealing their substantial role in complex traits.
Area of Science:
- Genomics
- Human Genetics
- Bioinformatics
Background:
- Structural variants (SVs) are a major source of genetic variation, yet their contribution to human traits is poorly understood due to genotyping challenges in large populations.
- Previous methods struggled to analyze SVs comprehensively across the genome in large cohorts.
Purpose of the Study:
- To develop a method for imputing structural variants (SVs) from single-nucleotide polymorphism (SNP) data to enable large-scale analysis.
- To investigate the role of SVs in complex human traits using genome-wide association studies (GWAS).
Main Methods:
- Generated a comprehensive catalog of 171,233 high-quality genome-wide SVs using PacBio HiFi long-read sequencing from 241 individuals.
- Developed ImputeSV, a reference panel and web application, to impute SVs from SNP data.
- Imputed 54,578 common SVs in 456,643 UK Biobank participants and performed GWAS for 2,624 traits.
Main Results:
- Demonstrated high accuracy for SV imputation at both individual and cohort levels.
- Estimated that SVs account for at least 4.7% of common genetic variation influencing complex traits.
- Identified 17,335 significant SV-trait associations, including 958 potentially driven by SVs rather than small variants.
Conclusions:
- Long-read sequencing data combined with imputation methods effectively enables large-scale SV analysis.
- Structural variants play a significant, previously underestimated role in the genetic architecture of complex human traits.
- The study provides a valuable resource of SVs and their associations within the UK Biobank cohort.
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...
03:36Genome Annotation and Assembly
The genome refers to all of the genetic material in an organism. It can range from a few million base pairs in microbial cells to several billion base pairs in many eukaryotic organisms. Genome assembly refers to the process of taking the DNA sequencing data and putting it all back together in a correct order to create a close representation of the original genome. This is followed by the identification of functional elements on the newly assembled genome, a process called genome annotation.
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%...
01:28Human Genetics
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
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,...
01:26Human Virome
The human body harbors a vast and diverse viral community known as the human virome. The virome includes bacteriophages that infect bacteria, and eukaryotic viruses that infect human cells. Transient dietary and environmental viruses also contribute to this dynamic ecosystem. Estimates suggest the human body may contain on the order of 10¹³ viral particles, though abundance varies widely by body site and detection method.Comprehensive characterization of the virome has become possible only with...