Genome partitioning of genetic variation for complex traits using common SNPs
Open accessAbstract
We estimate and partition genetic variation for height, body mass index (BMI), von Willebrand factor and QT interval (QTi) using 586,898 SNPs genotyped on 11,586 unrelated individuals. We estimate that ∼45%, ∼17%, ∼25% and ∼21% of the variance in height, BMI, von Willebrand factor and QTi, respectively, can be explained by all autosomal SNPs and a further ∼0.5-1% can be explained by X chromosome SNPs. We show that the variance explained by each chromosome is proportional to its length, and that SNPs in or near genes explain more variation than SNPs between genes. We propose a new approach to estimate variation due to cryptic relatedness and population stratification. Our results provide further evidence that a substantial proportion of heritability is captured by common SNPs, that height, BMI and QTi are highly polygenic traits, and that the additive variation explained by a part of the genome is approximately proportional to the total length of DNA contained within genes therein.
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Partitioning genetic variance by chromosome for diverse traits shows the proportion of variance explained is consistently proportional to chromosome length.
“partitioning of the genetic variance on a chromosome-by-chromosome basis, for a diverse set of traits, shows that the proportion of variance explained is consistently proportional to chromosome length75,76.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [75]
It is unclear whether the same methods are as efficient for schizophrenia, arthritis, or intelligence.
“and it is not clear that they are as efficient for schizophrenia, arthritis or intelligence75,76.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [75]
For BMI, those methods recover only about half or slightly more of the expected genotypic variance.
“Yet the same methods applied to BMI do not capture much more than half of the expected genotypic variance, and it is not clear that they are as efficient for schizophrenia, arthritis or intelligence75,76.”
From Rare and common variants: twenty arguments (2012) · cites this paper as [75]
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- Authors
- Yang, J., Manolio, T. A., Pasquale, L. R., Boerwinkle, E., Caporaso, N., Cunningham, J. M., de Andrade, M., Feenstra, B., Feingold, E., Hayes, M. G., Hill, W. G., Landi, M. T., Alonso, A., Lettre, G., Lin, P., Ling, H., Lowe, W., Mathias, R. A., Melbye, M., Pugh, E., Cornelis, M. C., Weir, B. S., Goddard, M. E., & Visscher, P. M.
- Affiliations
- QIMR Berghofer Medical Research Institute (AU)
- National Institutes of Health (US)
- Massachusetts Eye and Ear Infirmary (US)
- The University of Texas Health Science Center at Houston (US)
- Mayo Clinic (US)
- Statens Serum Institut (DK)
- University of Pittsburgh (US)
- Northwestern University (US)
- University of Edinburgh (GB)
- Montreal Heart Institute (CA)
- Washington University in St. Louis (US)
- Johns Hopkins University (US)
- Harvard University (US)
- University of Washington (US)
- The University of Melbourne (AU)
- Corresponding author
- Visscher, Peter M
- ORCID
- Venue
- Nature Genetics
- Published
- 2011-05-08
- Volume
- 43
- Issue
- 6
- Pages
- 519-525
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC4295936
- OpenAlex
- W2080235308
- Cited by
- 890
- References
- 46
- Citations by year
- 2026: 20 · 2025: 31 · 2024: 24 · 2023: 30 · 2022: 45 · 2021: 43 · 2020: 53 · 2019: 71 · 2018: 74 · 2017: 66 · 2016: 69 · 2015: 70 · 2014: 97 · 2013: 103 · 2012: 82
- FWCI
- 58.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Canadian Institutes of Health Research
- National Human Genome Research Institute (U01HG04424, U01HG004399, U01HG004402, U01HG004728, U01HG004446, U01HG004424)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- genome partitioning, common SNPs, complex traits, heritability, height, body mass index, von Willebrand factor, QT interval, polygenic traits, cryptic relatedness, population stratification, chromosome length, gene length, additive genetic variance
- MeSH terms
- Body Height, Chromosomes, Genetics, Population, Humans, Models, Genetic, Genetic Variation, von Willebrand Factor, Body Mass Index, Polymorphism, Single Nucleotide, Chromosomes, Human, X, X Chromosome Inactivation, Genome-Wide Association Study
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