267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation

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  • Joaquín Dopazo
  • Alicia Amadoz
  • Marta Bleda
  • Luz Garcia-Alonso
  • Alejandro Alemán
  • Francisco García-García
  • Josephine T. Daub
  • Gerard Muntané
  • Antonio Rueda
  • Alicia Vela-Boza
  • Francisco J. López-Domingo
  • Javier P. Florido
  • Pablo Arce
  • Macarena Ruiz-Ferrer
  • Cristina Méndez-Vidal
  • Todd E. Arnold
  • Olivia Spleiss
  • Miguel Alvarez-Tejado
  • Arcadi Navarro
  • Shomi S. Bhattacharya
  • Salud Borrego
  • Javier Santoyo-López
  • Guillermo Antiñolo

Recent results from large-scale genomic projects suggest that allele frequencies, which are highly relevant for medical purposes, differ considerably across different populations. The need for a detailed catalog of local variability motivated the whole-exome sequencing of 267 unrelated individuals, representative of the healthy Spanish population. Like in other studies, a considerable number of rare variants were found (almost one-third of the described variants). There were also relevant differences in allelic frequencies in polymorphic variants, including ∼10,000 polymorphisms private to the Spanish population. The allelic frequencies of variants conferring susceptibility to complex diseases (including cancer, schizophrenia, Alzheimer disease, type 2 diabetes, and other pathologies) were overall similar to those of other populations. However, the trend is the opposite for variants linked to Mendelian and rare diseases (including several retinal degenerative dystrophies and cardiomyopathies) that show marked frequency differences between populations. Interestingly, a correspondence between differences in allelic frequencies and disease prevalence was found, highlighting the relevance of frequency differences in disease risk. These differences are also observed in variants that disrupt known drug binding sites, suggesting an important role for local variability in population-specific drug resistances or adverse effects. We have made the Spanish population variant server web page that contains population frequency information for the complete list of 170,888 variant positions we found publicly available (http://spv.babelomics.org/), We show that it if fundamental to determine population-specific variant frequencies to distinguish real disease associations from population-specific polymorphisms.

Original languageEnglish
JournalMolecular Biology and Evolution
Issue number5
Pages (from-to)1205-1218
Number of pages14
Publication statusPublished - 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

    Research areas

  • disease variants, exome sequencing, pharmacogenomic variants, population variability

ID: 327400271