A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos
Abstract Background Association studies are useful to unravel the genetic basis of common human diseases. However, the presence of undetected population structure can lead to both false positive results and failures to detect genuine associations. Even when most of the approaches to deal with popula...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | BMC Genetics |
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| Online Access: | http://link.springer.com/article/10.1186/s12863-018-0707-7 |
| _version_ | 1818139341824720896 |
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| author | Alicia Huerta-Chagoya Hortensia Moreno-Macías Juan Carlos Fernández-López María Luisa Ordóñez-Sánchez Rosario Rodríguez-Guillén Alejandra Contreras Alfredo Hidalgo-Miranda Luis Alberto Alfaro-Ruíz Edgar Pavel Salazar-Fernandez Andrés Moreno-Estrada Carlos Alberto Aguilar-Salinas Teresa Tusié-Luna |
| author_facet | Alicia Huerta-Chagoya Hortensia Moreno-Macías Juan Carlos Fernández-López María Luisa Ordóñez-Sánchez Rosario Rodríguez-Guillén Alejandra Contreras Alfredo Hidalgo-Miranda Luis Alberto Alfaro-Ruíz Edgar Pavel Salazar-Fernandez Andrés Moreno-Estrada Carlos Alberto Aguilar-Salinas Teresa Tusié-Luna |
| author_sort | Alicia Huerta-Chagoya |
| collection | DOAJ |
| description | Abstract Background Association studies are useful to unravel the genetic basis of common human diseases. However, the presence of undetected population structure can lead to both false positive results and failures to detect genuine associations. Even when most of the approaches to deal with population stratification require genome-wide data, the use of a well-selected panel of ancestry informative markers (AIMs) may appropriately correct for population stratification. Few panels of AIMs have been developed for Latino populations and most contain a high number of markers (> 100 AIMs). For some association studies such as candidate gene approaches, it may be unfeasible to genotype a numerous set of markers to avoid false positive results. In such cases, methods that use fewer AIMs may be appropriate. Results We validated an accurate and cost-effective panel of AIMs, for use in population stratification correction of association studies and global ancestry estimation in Mexicans, as well as in populations having large proportions of both European and Native American ancestries. Based on genome-wide data from 1953 Mexican individuals, we performed a PCA and SNP weights were calculated to select subsets of unlinked AIMs within percentiles 0.10 and 0.90, ensuring that all chromosomes were represented. Correlations between PC1 calculated using genome-wide data versus each subset of AIMs (16, 32, 48 and 64) were r 2 = 0.923, 0.959, 0.972 and 0.978, respectively. When evaluating PCs performance as population stratification adjustment covariates, no correlation was found between P values obtained from uncorrected and genome-wide corrected association analyses (r 2 = 0.141), highlighting that population stratification correction is compulsory for association analyses in admixed populations. In contrast, high correlations were found when adjusting for both PC1 and PC2 for either subset of AIMs (r 2 > 0.900). After multiple validations, including an independent sample, we selected a minimal panel of 32 AIMs, which are highly informative of the major ancestral components of Mexican mestizos, namely European and Native American ancestries. Finally, the correlation between the global ancestry proportions calculated using genome-wide data and our panel of 32 AIMs was r 2 = 0.972. Conclusions Our panel of 32 AIMs accurately estimated global ancestry and corrected for population stratification in association studies in Mexican individuals. |
| first_indexed | 2024-12-11T10:26:33Z |
| format | Article |
| id | doaj.art-ba897d81a80f47dd95f13ef840a8f202 |
| institution | Directory Open Access Journal |
| issn | 1471-2156 |
| language | English |
| last_indexed | 2024-12-11T10:26:33Z |
| publishDate | 2019-01-01 |
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| series | BMC Genetics |
| spelling | doaj.art-ba897d81a80f47dd95f13ef840a8f2022022-12-22T01:11:08ZengBMCBMC Genetics1471-21562019-01-0120111110.1186/s12863-018-0707-7A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizosAlicia Huerta-Chagoya0Hortensia Moreno-Macías1Juan Carlos Fernández-López2María Luisa Ordóñez-Sánchez3Rosario Rodríguez-Guillén4Alejandra Contreras5Alfredo Hidalgo-Miranda6Luis Alberto Alfaro-Ruíz7Edgar Pavel Salazar-Fernandez8Andrés Moreno-Estrada9Carlos Alberto Aguilar-Salinas10Teresa Tusié-Luna11CONACYT, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránDepartamento de Economía, Universidad Autónoma MetropolitanaDepartamento de Genómica Computacional, Instituto Nacional de Medicina GenómicaUnidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránUnidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránInstituto Nacional de Medicina GenómicaLaboratorio de Genómica del Cáncer, Instituto Nacional de Medicina GenómicaLaboratorio de Genómica del Cáncer, Instituto Nacional de Medicina GenómicaLaboratorio Nacional de Genómica para la Biodiversidad (LANGEBIO-UGA), CINVESTAVLaboratorio Nacional de Genómica para la Biodiversidad (LANGEBIO-UGA), CINVESTAVDepartamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránUnidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránAbstract Background Association studies are useful to unravel the genetic basis of common human diseases. However, the presence of undetected population structure can lead to both false positive results and failures to detect genuine associations. Even when most of the approaches to deal with population stratification require genome-wide data, the use of a well-selected panel of ancestry informative markers (AIMs) may appropriately correct for population stratification. Few panels of AIMs have been developed for Latino populations and most contain a high number of markers (> 100 AIMs). For some association studies such as candidate gene approaches, it may be unfeasible to genotype a numerous set of markers to avoid false positive results. In such cases, methods that use fewer AIMs may be appropriate. Results We validated an accurate and cost-effective panel of AIMs, for use in population stratification correction of association studies and global ancestry estimation in Mexicans, as well as in populations having large proportions of both European and Native American ancestries. Based on genome-wide data from 1953 Mexican individuals, we performed a PCA and SNP weights were calculated to select subsets of unlinked AIMs within percentiles 0.10 and 0.90, ensuring that all chromosomes were represented. Correlations between PC1 calculated using genome-wide data versus each subset of AIMs (16, 32, 48 and 64) were r 2 = 0.923, 0.959, 0.972 and 0.978, respectively. When evaluating PCs performance as population stratification adjustment covariates, no correlation was found between P values obtained from uncorrected and genome-wide corrected association analyses (r 2 = 0.141), highlighting that population stratification correction is compulsory for association analyses in admixed populations. In contrast, high correlations were found when adjusting for both PC1 and PC2 for either subset of AIMs (r 2 > 0.900). After multiple validations, including an independent sample, we selected a minimal panel of 32 AIMs, which are highly informative of the major ancestral components of Mexican mestizos, namely European and Native American ancestries. Finally, the correlation between the global ancestry proportions calculated using genome-wide data and our panel of 32 AIMs was r 2 = 0.972. Conclusions Our panel of 32 AIMs accurately estimated global ancestry and corrected for population stratification in association studies in Mexican individuals.http://link.springer.com/article/10.1186/s12863-018-0707-7AIMAncestryPopulation stratificationAssociation studyMexican mestizos |
| spellingShingle | Alicia Huerta-Chagoya Hortensia Moreno-Macías Juan Carlos Fernández-López María Luisa Ordóñez-Sánchez Rosario Rodríguez-Guillén Alejandra Contreras Alfredo Hidalgo-Miranda Luis Alberto Alfaro-Ruíz Edgar Pavel Salazar-Fernandez Andrés Moreno-Estrada Carlos Alberto Aguilar-Salinas Teresa Tusié-Luna A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos BMC Genetics AIM Ancestry Population stratification Association study Mexican mestizos |
| title | A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos |
| title_full | A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos |
| title_fullStr | A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos |
| title_full_unstemmed | A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos |
| title_short | A panel of 32 AIMs suitable for population stratification correction and global ancestry estimation in Mexican mestizos |
| title_sort | panel of 32 aims suitable for population stratification correction and global ancestry estimation in mexican mestizos |
| topic | AIM Ancestry Population stratification Association study Mexican mestizos |
| url | http://link.springer.com/article/10.1186/s12863-018-0707-7 |
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