| Title: | Genomic partitioning of inbreeding depression in humans |
| Journal: | American Journal of Human Genetics |
| Published: | 1 Jul 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34214457/ |
| DOI: | https://doi.org/10.1016/j.ajhg.2021.06.005 |
| URL: | http://www.cell.com/article/S0002929721002299/pdf |
Publication 5073
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Across species, offspring of related individuals often exhibit significant reduction in fitness-related traits, known as inbreeding depression (ID), yet the genetic and molecular basis for ID remains elusive. Here, we develop a method to quantify enrichment of ID within specific genomic annotations and apply it to human data. We analyzed the phenomes and genomes of ∼350,000 unrelated participants of the UK Biobank and found, on average of over 11 traits, significant enrichment of ID within genomic regions with high recombination rates (>21-fold; p < 10-5), with conserved function across species (>19-fold; p < 10-4), and within regulatory elements such as DNase I hypersensitive sites (∼5-fold; p = 8.9 × 10-7). We also quantified enrichment of ID within trait-associated regions and found suggestive evidence that genomic regions contributing to additive genetic variance in the population are enriched for ID signal. We find strong correlations between functional enrichment of SNP-based heritability and that of ID (r = 0.8, standard error: 0.1). These findings provide empirical evidence that ID is most likely due to many partially recessive deleterious alleles in low linkage disequilibrium regions of the genome. Our study suggests that functional characterization of ID may further elucidate the genetic architectures and biological mechanisms underlying complex traits and diseases.</p>
6 Authors
- Loic Yengo
- Jian Yang
- Matthew C Keller
- Michael E Goddard
- Naomi R Wray
- Peter M Visscher
Enabling scientific discoveries that improve human health