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Published on: June 21, 2018
Genome partitioning of genetic variation for complex traits using common SNPs.
Jian Yang1, Teri A Manolio, Louis R Pasquale
1Queensland Statistical Genetics Laboratory, Queensland Institute of Medical Research, Brisbane, Australia.
Nature Genetics
|May 10, 2011
Summary
Common genetic variants explain significant trait variation, with height, BMI, and QTi being highly polygenic. Genetic contribution of each chromosome is proportional to its length, and genes influence variation more than intergenic regions.
Area of Science:
- Human genetics
- Quantitative trait genomics
- Statistical genetics
Background:
- Understanding the genetic architecture of complex human traits is crucial for advancing personalized medicine and disease risk prediction.
- Previous studies have identified numerous genetic loci associated with common traits, but the total variation explained by common single nucleotide polymorphisms (SNPs) remains an active area of research.
Purpose of the Study:
- To estimate and partition the genetic variation for four key human traits: height, body mass index (BMI), von Willebrand factor, and QT interval (QTi).
- To investigate the relationship between chromosomal length and the proportion of variance explained by SNPs.
- To assess the contribution of SNPs located within or near genes versus those in intergenic regions.
Main Methods:
- Utilized genome-wide genotype data from 586,898 SNPs across 11,586 unrelated individuals.
- Employed a linear mixed model approach to estimate SNP-based heritability and partition genetic variance.
- Developed and applied a novel method to account for cryptic relatedness and population stratification.
Main Results:
- Common autosomal SNPs explained approximately 45% of height variance, 17% of BMI variance, 25% of von Willebrand factor variance, and 21% of QTi variance.
- X chromosome SNPs contributed an additional 0.5-1% to the explained variance for these traits.
- The proportion of variance explained by each chromosome was found to be proportional to its physical length, and SNPs within genes explained more variation than intergenic SNPs.
Conclusions:
- A substantial portion of the heritability for height, BMI, von Willebrand factor, and QTi is captured by common SNPs.
- These traits are highly polygenic, indicating that many genes contribute small effects.
- The additive genetic variation explained by a genomic region is approximately proportional to the length of DNA within genes in that region.
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