TY - JOUR

T1 - 267 Spanish Exomes Reveal Population-Specific Differences in Disease-Related Genetic Variation

AU - Dopazo, Joaquín

AU - Amadoz, Alicia

AU - Bleda, Marta

AU - Garcia-Alonso, Luz

AU - Alemán, Alejandro

AU - García-García, Francisco

AU - Rodriguez, Juan A.

AU - Daub, Josephine T.

AU - Muntané, Gerard

AU - Rueda, Antonio

AU - Vela-Boza, Alicia

AU - López-Domingo, Francisco J.

AU - Florido, Javier P.

AU - Arce, Pablo

AU - Ruiz-Ferrer, Macarena

AU - Méndez-Vidal, Cristina

AU - Arnold, Todd E.

AU - Spleiss, Olivia

AU - Alvarez-Tejado, Miguel

AU - Navarro, Arcadi

AU - Bhattacharya, Shomi S.

AU - Borrego, Salud

AU - Santoyo-López, Javier

AU - Antiñolo, Guillermo

N1 - Publisher Copyright: © 2016 The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - disease variants

KW - exome sequencing

KW - pharmacogenomic variants

KW - population variability

U2 - 10.1093/molbev/msw005

DO - 10.1093/molbev/msw005

M3 - Journal article

C2 - 26764160

AN - SCOPUS:84962880144

VL - 33

SP - 1205

EP - 1218

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 5

ER -