Cargando…
Recent human evolution has shaped geographical differences in susceptibility to disease
BACKGROUND: Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-ba...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039608/ https://www.ncbi.nlm.nih.gov/pubmed/21261943 http://dx.doi.org/10.1186/1471-2164-12-55 |
_version_ | 1782198205651353600 |
---|---|
author | Marigorta, Urko M Lao, Oscar Casals, Ferran Calafell, Francesc Morcillo-Suárez, Carlos Faria, Rui Bosch, Elena Serra, François Bertranpetit, Jaume Dopazo, Hernán Navarro, Arcadi |
author_facet | Marigorta, Urko M Lao, Oscar Casals, Ferran Calafell, Francesc Morcillo-Suárez, Carlos Faria, Rui Bosch, Elena Serra, François Bertranpetit, Jaume Dopazo, Hernán Navarro, Arcadi |
author_sort | Marigorta, Urko M |
collection | PubMed |
description | BACKGROUND: Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies. RESULTS: We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. CONCLUSIONS: Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations. |
format | Text |
id | pubmed-3039608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-30396082011-02-16 Recent human evolution has shaped geographical differences in susceptibility to disease Marigorta, Urko M Lao, Oscar Casals, Ferran Calafell, Francesc Morcillo-Suárez, Carlos Faria, Rui Bosch, Elena Serra, François Bertranpetit, Jaume Dopazo, Hernán Navarro, Arcadi BMC Genomics Research Article BACKGROUND: Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies. RESULTS: We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. CONCLUSIONS: Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations. BioMed Central 2011-01-24 /pmc/articles/PMC3039608/ /pubmed/21261943 http://dx.doi.org/10.1186/1471-2164-12-55 Text en Copyright ©2011 Marigorta et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Marigorta, Urko M Lao, Oscar Casals, Ferran Calafell, Francesc Morcillo-Suárez, Carlos Faria, Rui Bosch, Elena Serra, François Bertranpetit, Jaume Dopazo, Hernán Navarro, Arcadi Recent human evolution has shaped geographical differences in susceptibility to disease |
title | Recent human evolution has shaped geographical differences in susceptibility to disease |
title_full | Recent human evolution has shaped geographical differences in susceptibility to disease |
title_fullStr | Recent human evolution has shaped geographical differences in susceptibility to disease |
title_full_unstemmed | Recent human evolution has shaped geographical differences in susceptibility to disease |
title_short | Recent human evolution has shaped geographical differences in susceptibility to disease |
title_sort | recent human evolution has shaped geographical differences in susceptibility to disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3039608/ https://www.ncbi.nlm.nih.gov/pubmed/21261943 http://dx.doi.org/10.1186/1471-2164-12-55 |
work_keys_str_mv | AT marigortaurkom recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT laooscar recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT casalsferran recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT calafellfrancesc recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT morcillosuarezcarlos recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT fariarui recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT boschelena recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT serrafrancois recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT bertranpetitjaume recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT dopazohernan recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease AT navarroarcadi recenthumanevolutionhasshapedgeographicaldifferencesinsusceptibilitytodisease |