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Cited by 43Genetic and phenotypic traits in livestockGenetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and Animals

Phenotypic covariance across the entire spectrum of relatedness for 86 billion pairs of individuals

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Kemper, Kathryn E., Yengo, Loic, Zheng, Zhili, Abdellaoui, Abdel, Keller, Matthew C., Goddard, Michael E., Wray, Naomi R., Yang, Jian +1 more·2021·Nature Communications
DOI 10.1038/s41467-021-21283-4PMC PMC7886899
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Abstract

Attributing the similarity between individuals to genetic and non-genetic factors is central to genetic analyses. In this paper we use the genomic relationship ($$\pi$$π) among 417,060 individuals to investigate the phenotypic covariance between pairs of individuals for 32 traits across the spectrum of relatedness, from unrelated pairs through to identical twins. We find linear relationships between phenotypic covariance and$$\pi$$πthat agree with the SNP-based heritability ($$\hat h_{SNP}^2$$ĥSNP2) in unrelated pairs ($$\pi \, < \, 0.02$$π<0.02), and with pedigree-estimated heritability in close relatives ($$\pi \, > \, 0.05$$π>0.05). The covariance increases faster than$$\pi \hat h_{SNP}^2$$πĥSNP2in distant relatives ($$0.02 \, > \, \pi \, > \, 0.05$$0.02>π>0.05), and we attribute this to imperfect linkage disequilibrium between causal variants and the common variants used to construct$$\pi$$π. We also examine the effect of assortative mating on heritability estimates from different experimental designs. We find that full-sib identity-by-descent regression estimates for height (0.66 s.e. 0.07) are consistent with estimates from close relatives (0.82 s.e. 0.04) after accounting for the effect of assortative mating.

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  • DGE-based SNP heritability estimates do not account for the increase in genetic variance due to AM-induced correlations between causal alleles, leading to a downward bias similar to other family-based heritability estimates.

    “However, DGE-based SNP heritability estimates do not account for the increase in genetic variance due to AM-induced correlations between causal alleles, leading to a downward bias similar to other family-based heritability estimates such as classical twin designs and relatedness disequilibrium regression23,36.”

    From Family-GWAS reveals effects of environment and mating on genetic associations (2024) · cites this paper as [36]

    The Introduction says assortative mating correlates causal variants and increases genetic variance. Results > Adjusting parameter estimates for assortative mating says classical twin and full-sib estimates do not equal equilibrium heritability under assortative mating, and the Discussion extends this interpretation to relatedness disequilibrium regression. The paper does not establish that DGE-based SNP heritability specifically excludes that added variance or is downward-biased for that reason; it describes a separate limitation of SNP heritability, imperfect tagging of causal variants. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • While assortative mating is unlikely to affect within-sibship GWAS estimates, it can bias within-sibship estimates of heritability downwards and so may have affected the LDSC SNP heritability and genetic correlation estimates.

    “Another limitation is that while assortative mating is unlikely to affect within-sibship GWAS estimates, it can bias within-sibship estimates of heritability downwards49 and so may have affected our LDSC SNP heritability and genetic correlation estimates.”

    From Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects (2022) · cites this paper as [49]

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Authors
Kemper, K. E., Yengo, L., Zheng, Z., Abdellaoui, A., Keller, M. C., Goddard, M. E., Wray, N. R., Yang, J., & Visscher, P. M.
Affiliations
  • The University of Queensland (AU)
  • Amsterdam University Medical Centers (NL)
  • University of Colorado Boulder (US)
  • The University of Melbourne (AU)
Corresponding author
  • Kemper, Kathryn E.
  • Visscher, Peter M.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2021-02-16
Volume
12
Issue
1
Pages
1050-1050
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-021-21283-4
PMC
PMC7886899
OpenAlex
W3131877806
Cited by
43
References
48
Citations by year
2026: 8 · 2025: 11 · 2024: 7 · 2023: 3 · 2022: 10 · 2021: 4
FWCI
3.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Pure Amsterdam UMC (acceptedVersion, cc-by)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
  • National Institutes of Health
  • Medical Research Council (1107258, 1113400, 1127440, 1103418)
  • Australian Research Council (FL180100072, DP160102400, 1113400, FT180100186)
  • National Health and Medical Research Council (1113400, 1127440, 1107258, 1103418)
  • National Institute on Aging (R01AG042568)
  • National Institute of Mental Health (R01MH100141)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords
phenotypic covariance, genomic relationships, heritability, relatedness, linkage disequilibrium, assortative mating, identity by descent, height, common genetic variants, genetic similarity
MeSH terms
Adult, Aged, Educational Status, United Kingdom, Humans, Middle Aged, Models, Genetic, Phenotype, Phylogeny, Regression Analysis, Linkage Disequilibrium, Genome, Human, Body Mass Index, Biological Specimen Banks, Quantitative Trait, Heritable, Polymorphism, Single Nucleotide, Inheritance Patterns

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