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Revisiting heritability accounting for shared environmental effects and maternal inheritance

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Abstract

Heritability measures the proportion of phenotypic variation attributable to genetic factors. In addition to a shared nuclear genetic component, a number of additional variance components, such as spousal correlation, sibship, household and maternal effects, may have strong contributions to inter-individual phenotype variation. In humans, the confounding effects of these components on heritability have not been studied thoroughly. We sought to obtain unbiased heritability estimates for complex traits in the presence of multiple variance components and also to estimate the contributions of these variance components to complex traits. We compared regression and variance component methods to estimate heritability in simulations when additional variance components existed. We then revisited heritability for several traits in Framingham Heart Study (FHS) participants. Using simulations, we found that failure to account for or misclassification of necessary variance components yielded biased heritability estimates. The direction and magnitude of the bias varied depending on a variance structure and an estimation method. Using the best fitted models to account for necessary variance components, we found that heritability estimates for most FHS traits were overestimated, ranging from 4 to 47 %, when we compared models that considered necessary variance components to models that only considered familial relationships. Spousal correlation explained 14–36 % of phenotypic variation in several anthropometric and lifestyle traits. Maternal and sibling effects also contributed to phenotypic variation, ranging from 3 to 5 % and 4 to 7 %, respectively, in several anthropometric and metabolic traits. Our findings may explain, in part, the missing heritability for some traits.

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Acknowledgments

We acknowledge support from NHLBI, Framingham Heart Study, (NHLBI/NIH Contract #N01-HC-25195), from NIH NIDDK R01 DK078616 and K24 DK080140, from the Boston University School of Medicine, and from contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture, Agriculture Research Service. We thank Dr. Qiong Yang of Biostatistics, School of Public Health at Boston University for helpful discussions and Dr. Kathryn Lunetta of Biostatistics, School of Public Health at Boston University for providing R codes for incorporating additional variance components in lmekin () function.

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Authors and Affiliations

  1. The Framingham Heart Study, Framingham, MA, 01702, USA

    Chunyu Liu, Josée Dupuis, Martin G. Larson, L. Adrienne Cupples, Ramachandran S. Vasan & Daniel Levy

  2. Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Chunyu Liu & Daniel Levy

  3. Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA

    Josée Dupuis, Martin G. Larson & L. Adrienne Cupples

  4. Department of Mathematics and Statistics, Boston University, Boston, MA, 02215, USA

    Martin G. Larson

  5. Nutrition and Genomics Laboratory, Jean Mayer USDA HNRCA at Tufts University, Boston, MA, 02111, USA

    Jose M. Ordovas

  6. Department of Medicine, Boston University, Boston, MA, 02118, USA

    Ramachandran S. Vasan

  7. General Medicine Division, Massachusetts General Hospital, Boston, MA, 02114, USA

    James B. Meigs

  8. Harvard Medical School, Boston, MA, 02114, USA

    James B. Meigs

  9. Nutritional Epidemiology Program, Jean Mayer USDA HNRCA at Tufts University, Boston, MA, 02111, USA

    Paul F. Jacques

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  1. Chunyu Liu
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  9. Daniel Levy
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Correspondence to Chunyu Liu.

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Liu, C., Dupuis, J., Larson, M.G. et al. Revisiting heritability accounting for shared environmental effects and maternal inheritance. Hum Genet 134, 169–179 (2015). https://doi.org/10.1007/s00439-014-1505-6

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  • DOI: https://doi.org/10.1007/s00439-014-1505-6

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