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The collective effects of genetic variants and complex traits

Journal of Human Genetics volume 68, pages 255–262 (2023)Cite this article

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Abstract

Traditional approaches in studying the genetics of complex traits have focused on identifying specific genetic variants. However, the collective effects of variants have remained largely unexplored. Here, we evaluated whether traits could be influenced by the collective effects of variants across the entire protein coding-region of the genome or the entire genome. We studied the UK Biobank exome sequencing data of 167,246 individuals as well as the genome-wide SNP array data of 408,868 individuals. We calculated for each individual four different measures of genetic variation such as heterozygosity and number of variants and two different measures of the overall deleteriousness of all variants, and performed correlations with 17 representative traits that have been studied previously. Linear regression analysis was performed with adjustment for age, sex, and genetic principal components. The results showed a high correlation among the six different measures and an inverse association of two well-correlated traits (educational attainment and height) with the total number of all variants as well as the overall deleteriousness of all variants. We have also categorized the genes based on whether they are expressed in the brain and found that the association with educational attainment only held for the brain-expressed genes. No other traits examined showed a significant correlation with the brain-expressed genes. The study demonstrates that common traits could be studied by analyzing the overall genetic variation and suggests that educational attainment is inversely related to genetic variation.

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Acknowledgements

Supported by the National Natural Science Foundation of China grant 81171880 (SH).

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Authors and Affiliations

  1. Center for Medical Genetics, Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, 110 Xiangya Road, Changsha, Hunan, 410078, PR China

    Mingrui Wang & Shi Huang

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  1. Mingrui Wang
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  2. Shi Huang
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Contributions

MW and SH devised the project, performed data analysis, and wrote and edited the manuscript.

Corresponding author

Correspondence to Shi Huang.

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The authors declare no competing interests.

Ethical approval

This study utilized deidentified data from the baseline assessment of the UK Biobank, a prospective cohort study of 500,000 individuals (age 40–69 years) recruited across Great Britain during 2006–2010. UK Biobank had obtained ethics approval from the North West Multi-centre Research Ethics Committee, which covers the UK (approval number: 11/NW/0382) and had obtained informed consent from all participants. The UK Biobank approved an application for use of the data (ID 18051).

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Wang, M., Huang, S. The collective effects of genetic variants and complex traits. J Hum Genet 68, 255–262 (2023). https://doi.org/10.1038/s10038-022-01105-1

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