35 results on '"Granja, Vanessa"'
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2. Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape
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Li, Qing, Chen, Jieyi, Faux, Pierre, Delgado, Miguel Eduardo, Bonfante, Betty, Fuentes-Guajardo, Macarena, Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Everardo-Martínez, Paola, Sánchez-Quinto, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Wu, Sijie, Du, Siyuan, Giardina, Andrea, Paria, Soumya Subhra, Khokan, Mahfuzur Rahman, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Rojas, Winston, Rothhammer, Francisco, Navarro, Nicolas, Wang, Sijia, Adhikari, Kaustubh, and Ruiz-Linares, Andrés
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- 2023
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3. Prediction of eye, hair and skin colour in Latin Americans
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Palmal, Sagnik, Adhikari, Kaustubh, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Silva de Cerqueira, Caio Cesar, Bonfante, Betty, Chacón-Duque, Juan Camilo, Sohail, Anood, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo-Martínez, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Parolin, Maria-Laura, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Faux, Pierre, and Ruiz-Linares, Andrés
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- 2021
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4. A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia
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Adhikari, Kaustubh, Mendoza-Revilla, Javier, Sohail, Anood, Fuentes-Guajardo, Macarena, Lampert, Jodie, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hunemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Salzano, Francisco M., Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Tobin, Desmond J., Fumagalli, Matteo, Balding, David, and Ruiz-Linares, Andrés
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- 2019
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5. Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance
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Chacón-Duque, Juan-Camilo, Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Mendoza-Revilla, Javier, Acuña-Alonzo, Victor, Barquera, Rodrigo, Quinto-Sánchez, Mirsha, Gómez-Valdés, Jorge, Everardo Martínez, Paola, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Villena, Mercedes, Vásquez, René, Llop, Elena, Sandoval, José R., Salazar-Granara, Alberto A., Parolin, Maria-Laura, Sandoval, Karla, Peñaloza-Espinosa, Rosenda I., Rangel-Villalobos, Hector, Winkler, Cheryl A., Klitz, William, Bravi, Claudio, Molina, Julio, Corach, Daniel, Barrantes, Ramiro, Gomes, Verónica, Resende, Carlos, Gusmão, Leonor, Amorim, Antonio, Xue, Yali, Dugoujon, Jean-Michel, Moral, Pedro, González-José, Rolando, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Poletti, Giovanni, Gallo, Carla, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Hellenthal, Garrett, and Ruiz-Linares, Andrés
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- 2018
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6. Disentangling Signatures of Selection Before and After European Colonization in Latin Americans
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Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Fuentes-Guajardo, Macarena, Ormond, Louise, Wang, Ke, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, de Cerqueira, Caio C. Silva, Rivera, Keyla M. Badillo, Nieves-Colón, Maria A., Gignoux, Christopher R., Wojcik, Genevieve L., Moreno-Estrada, Andrés, Hünemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Fumagalli, Matteo, Adhikari, Kaustubh, Ruiz-Linares, Andrés, Hellenthal, Garrett, Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Fuentes-Guajardo, Macarena, Ormond, Louise, Wang, Ke, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, de Cerqueira, Caio C. Silva, Rivera, Keyla M. Badillo, Nieves-Colón, Maria A., Gignoux, Christopher R., Wojcik, Genevieve L., Moreno-Estrada, Andrés, Hünemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Fumagalli, Matteo, Adhikari, Kaustubh, Ruiz-Linares, Andrés, and Hellenthal, Garrett
- Abstract
Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
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- 2022
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7. Disentangling Signatures of Selection Before and After European Colonization in Latin Americans
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Mendoza-Revilla, Javier, primary, Chacón-Duque, J. Camilo, additional, Fuentes-Guajardo, Macarena, additional, Ormond, Louise, additional, Wang, Ke, additional, Hurtado, Malena, additional, Villegas, Valeria, additional, Granja, Vanessa, additional, Acuña-Alonzo, Victor, additional, Jaramillo, Claudia, additional, Arias, William, additional, Barquera, Rodrigo, additional, Gómez-Valdés, Jorge, additional, Villamil-Ramírez, Hugo, additional, Silva de Cerqueira, Caio C., additional, Badillo Rivera, Keyla M., additional, Nieves-Colón, Maria A., additional, Gignoux, Christopher R., additional, Wojcik, Genevieve L., additional, Moreno-Estrada, Andrés, additional, Hünemeier, Tábita, additional, Ramallo, Virginia, additional, Schuler-Faccini, Lavinia, additional, Gonzalez-José, Rolando, additional, Bortolini, Maria-Cátira, additional, Canizales-Quinteros, Samuel, additional, Gallo, Carla, additional, Poletti, Giovanni, additional, Bedoya, Gabriel, additional, Rothhammer, Francisco, additional, Balding, David, additional, Fumagalli, Matteo, additional, Adhikari, Kaustubh, additional, Ruiz-Linares, Andrés, additional, and Hellenthal, Garrett, additional
- Published
- 2022
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8. Fully automatic landmarking of 2D photographs identifies novel genetic loci influencing facial features
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Li, Qing, primary, Chen, Jieyi, additional, Faux, Pierre, additional, Bonfante, Betty, additional, Fuentes-Guajardo, Macarena, additional, Mendoza-Revilla, Javier, additional, Chacón-Duque, Juan, additional, Hurtado, Malena, additional, Villegas, Valeria, additional, Granja, Vanessa, additional, Jaramillo, Claudia, additional, Arias, William, additional, Barquera, Rodrigo, additional, Everardo-Martínez, Paola, additional, Sánchez-Quinto, Mirsha, additional, Gómez-Valdés, Jorge, additional, Villamil-Ramírez, Hugo, additional, de Cerqueira, Caio C. Silva, additional, Hünemeier, Tábita, additional, Ramallo, Virginia, additional, Wu, Sijie, additional, Du, Siyuan, additional, Gonzalez-José, Rolando, additional, Schüler-Faccini, Lavinia, additional, Bortolini, Maria-Cátira, additional, Acuña-Alonzo, Victor, additional, Canizales-Quinteros, Samuel, additional, Gallo, Carla, additional, Poletti, Giovanni, additional, Rojas, Winston, additional, Rothhammer, Francisco, additional, Navarro, Nicolas, additional, Wang, Sijia, additional, Adhikari, Kaustubh, additional, and Ruiz-Linares, Andrés, additional
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- 2022
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9. Disentangling signatures of selection before and after European colonization in Latin Americans
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Mendoza-Revilla, Javier, primary, Chacón-Duque, Juan Camilo, additional, Fuentes-Guajardo, Macarena, additional, Ormond, Louise, additional, Wang, Ke, additional, Hurtado, Malena, additional, Villegas, Valeria, additional, Granja, Vanessa, additional, Acuña-Alonzo, Victor, additional, Jaramillo, Claudia, additional, Arias, William, additional, Lozano, Rodrigo Barquera, additional, Gómez-Valdés, Jorge, additional, Villamil-Ramírez, Hugo, additional, Silva de Cerqueira, Caio C., additional, Badillo Rivera, Keyla M., additional, Nieves-Colón, Maria A., additional, Gignoux, Christopher R., additional, Wojcik, Genevieve L., additional, Moreno-Estrada, Andrés, additional, Hunemeier, Tábita, additional, Ramallo, Virginia, additional, Schuler-Faccini, Lavinia, additional, Gonzalez-José, Rolando, additional, Bortolini, Maria-Cátira, additional, Canizales-Quinteros, Samuel, additional, Gallo, Carla, additional, Poletti, Giovanni, additional, Bedoya, Gabriel, additional, Rothhammer, Francisco, additional, Balding, David, additional, Fumagalli, Matteo, additional, Adhikari, Kaustubh, additional, Ruiz-Linares, Andrés, additional, and Hellenthal, Garrett, additional
- Published
- 2021
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10. A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation
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Bonfante, Betty, primary, Faux, Pierre, additional, Navarro, Nicolas, additional, Mendoza-Revilla, Javier, additional, Dubied, Morgane, additional, Montillot, Charlotte, additional, Wentworth, Emma, additional, Poloni, Lauriane, additional, Varón-González, Ceferino, additional, Jones, Philip, additional, Xiong, Ziyi, additional, Fuentes-Guajardo, Macarena, additional, Palmal, Sagnik, additional, Chacón-Duque, Juan Camilo, additional, Hurtado, Malena, additional, Villegas, Valeria, additional, Granja, Vanessa, additional, Jaramillo, Claudia, additional, Arias, William, additional, Barquera, Rodrigo, additional, Everardo-Martínez, Paola, additional, Sánchez-Quinto, Mirsha, additional, Gómez-Valdés, Jorge, additional, Villamil-Ramírez, Hugo, additional, Silva de Cerqueira, Caio C., additional, Hünemeier, Tábita, additional, Ramallo, Virginia, additional, Liu, Fan, additional, Weinberg, Seth M., additional, Shaffer, John R., additional, Stergiakouli, Evie, additional, Howe, Laurence J., additional, Hysi, Pirro G., additional, Spector, Timothy D., additional, Gonzalez-José, Rolando, additional, Schüler-Faccini, Lavinia, additional, Bortolini, Maria-Cátira, additional, Acuña-Alonzo, Victor, additional, Canizales-Quinteros, Samuel, additional, Gallo, Carla, additional, Poletti, Giovanni, additional, Bedoya, Gabriel, additional, Rothhammer, Francisco, additional, Thauvin-Robinet, Christel, additional, Faivre, Laurence, additional, Costedoat, Caroline, additional, Balding, David, additional, Cox, Timothy, additional, Kayser, Manfred, additional, Duplomb, Laurence, additional, Yalcin, Binnaz, additional, Cotney, Justin, additional, Adhikari, Kaustubh, additional, and Ruiz-Linares, Andrés, additional
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- 2021
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11. Prediction of Eye, Hair and Skin Color in Admixed Populations of Latin America
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Palmal, Sagnik, primary, Adhikari, Kaustubh, additional, Mendoza-Revilla, Javier, additional, Fuentes-Guajardo, Macarena, additional, de Cerqueira, Caio C. Silva, additional, Chacón-Duque, Juan Camilo, additional, Sohail, Anood, additional, Hurtado, Malena, additional, Villegas, Valeria, additional, Granja, Vanessa, additional, Jaramillo, Claudia, additional, Arias, William, additional, Lozano, Rodrigo Barquera, additional, Everardo-Martínez, Paola, additional, Gómez-Valdés, Jorge, additional, Villamil-Ramírez, Hugo, additional, Hünemeier, Tábita, additional, Ramallo, Virginia, additional, Gonzalez-José, Rolando, additional, Schüler-Faccini, Lavinia, additional, Bortolini, Maria-Cátira, additional, Acuña-Alonzo, Victor, additional, Canizales-Quinteros, Samuel, additional, Gallo, Carla, additional, Poletti, Giovanni, additional, Bedoya, Gabriel, additional, Rothhammer, Francisco, additional, Balding, David, additional, Faux, Pierre, additional, and Ruiz-Linares, Andrés, additional
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- 2020
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12. Latin Americans show wide-spread Converso ancestry and the imprint of local Native ancestry on physical appearance
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Chacon-Duque, Juan C., primary, Adhikari, Kaustubh, additional, Fuentes-Guajardo, Macarena, additional, Mendoza-Revilla, Javier, additional, Acunñ-Alonzo, Victor, additional, Barquera Lozano, Rodrigo, additional, Quinto-Sánchez, Mirsha, additional, Gómez-Valdés, Jorge, additional, Everardo Martínez, Paola, additional, Villamil-Ramírez, Hugo, additional, Hünemeier, Tábita, additional, Ramallo, Virginia, additional, Silva de Cerqueira, Caio C., additional, Hurtado, Malena, additional, Villegas, Valeria, additional, Granja, Vanessa, additional, Villena, Mercedes, additional, Vásquez, René, additional, Llop, Elena, additional, Sandoval, José R., additional, Salazar-Granara, Alberto A., additional, Parolin, Maria-Laura, additional, Sandoval, Karla, additional, Peñaloza-Espinosa, Rosenda I., additional, Rangel-Villalobos, Hector, additional, Winkler, Cheryl, additional, Klitz, William, additional, Bravi, Claudio, additional, Molina, Julio, additional, Corach, Daniel, additional, Barrantes, Ramiro, additional, Gomes, Verónica, additional, Resende, Carlos, additional, Gusmão, Leonor, additional, Amorim, Antonio, additional, Xue, Yali, additional, Dugoujon, Jean-Michel, additional, Moral, Pedro, additional, Gonzalez-José, Rolando, additional, Schuler-Faccini, Lavinia, additional, Salzano, Francisco M., additional, Bortolini, Maria-Cátira, additional, Canizales-Quinteros, Samuel, additional, Poletti, Giovanni, additional, Gallo, Carla, additional, Bedoya, Gabriel, additional, Rothhammer, Francisco, additional, Balding, David, additional, Hellenthal, Garrett, additional, and Ruiz-Linares, Andres, additional
- Published
- 2018
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13. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation
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Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Quinto-Sánchez, Mirsha, Mendoza-Revilla, Javier, Camilo Chacón-Duque, Juan, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Pérez, Gastón Macín, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Cheeseman, Michael, Rosique, Javier, Bedoya, Gabriel, Rothhammer, Francisco, Headon, Denis, González-José, Rolando, Balding, David, and Ruiz-Linares, Andrés
- Subjects
Adult ,Population genetics ,Science ,purl.org/pe-repo/ocde/ford#1.06.03 [https] ,Otras Ciencias Biológicas ,purl.org/pe-repo/ocde/ford#1.03.00 [https] ,Cadherin Related Proteins ,morphogenesis ,Core Binding Factor Alpha 1 Subunit ,Nerve Tissue Proteins ,Paired Box Transcription Factors/genetics ,Polymorphism, Single Nucleotide ,Article ,purl.org/becyt/ford/1 [https] ,Core Binding Factor Alpha 1 Subunit/genetics ,Ciencias Biológicas ,Mice ,Young Adult ,Zinc Finger Protein Gli3 ,Paired Box Transcription Factors ,Animals ,Humans ,Nerve Tissue Proteins/genetics ,purl.org/becyt/ford/1.6 [https] ,Maxillofacial Development ,Edar Receptor ,Maxillofacial Development/genetics ,Anatomic Variation ,Zinc Finger Protein Gli3/genetics ,Edar Receptor/genetics ,stomatognathic diseases ,Latin America ,Cadherin Related Proteins/genetics ,Face ,genome-wide association studies ,purl.org/pe-repo/ocde/ford#1.04.00 [https] ,Face/anatomy & histology ,CIENCIAS NATURALES Y EXACTAS ,Genome-Wide Association Study - Abstract
We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values, Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci (RUNX2, GLI3, DCHS2 and PAX1) influencing nose morphology.
- Published
- 2016
14. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features
- Author
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Adhikari, Kaustubh, Fontanil, Tania, Cal, Santiago, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Chacón-Duque, Juan-Camilo, Al-Saadi, Farah, Johansson, Jeanette A., Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Gonzalez-José, Rolando, Headon, Denis, López-Otín, Carlos, Tobin, Desmond J., Balding, David, and Ruiz-Linares, Andrés
- Subjects
Male ,Science ,Otras Ciencias Biológicas ,purl.org/pe-repo/ocde/ford#1.06.03 [https] ,purl.org/pe-repo/ocde/ford#1.03.00 [https] ,Article ,purl.org/becyt/ford/1 [https] ,Ciencias Biológicas ,Scalp/physiology ,Humans ,purl.org/becyt/ford/1.6 [https] ,Scalp ,integumentary system ,Continental Population Groups ,Gene Expression Regulation/physiology ,Racial Groups ,population genetics ,Genetic Variation ,Face/physiology ,Gene Expression Regulation ,Face ,genome-wide association studies ,purl.org/pe-repo/ocde/ford#1.04.00 [https] ,Female ,sense organs ,CIENCIAS NATURALES Y EXACTAS ,Hair ,Genome-Wide Association Study ,Hair/growth & development - Abstract
We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair., By examining Latin American individuals of mixed European, Native American and African ancestry, Adhikari et al. identify novel loci influencing various features of facial and scalp hair. The study also provides experimental evidence that one of the implicated genes (PRSS53) is expressed in the hair follicle and that the top associated variant alters processing of this enzyme.
- Published
- 2016
15. A genome-wide association study identifies multiple loci for variation in human ear morphology
- Author
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Adhikari, Kaustubh, Reales, Guillermo, Smith, Andrew J. P., Konka, Esra, Palmen, Jutta, Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Fuentes, Macarena, Pizarro, María, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Calderón, Rosario, Rosique, Javier, Cheeseman, Michael, Bhutta, Mahmood F., Humphries, Steve E., Gonzalez-José, Rolando, Headon, Denis, Balding, David, and Ruiz-Linares, Andrés
- Subjects
Adult ,Male ,Adolescent ,Genotype ,purl.org/pe-repo/ocde/ford#1.06.03 [https] ,purl.org/pe-repo/ocde/ford#1.03.00 [https] ,Polymorphism, Single Nucleotide ,Article ,White People ,Ciencias Biológicas ,purl.org/becyt/ford/1 [https] ,Genética y Herencia ,Mice ,Young Adult ,Cell Line, Tumor ,Morphogenesis ,Homeodomain Proteins/metabolism ,Animals ,Humans ,European Continental Ancestry Group/genetics ,purl.org/becyt/ford/1.6 [https] ,American Indian or Alaska Native ,T-Box Domain Proteins/genetics/metabolism ,pinna morphology ,Homeodomain Proteins ,American Native Continental Ancestry Group/genetics ,Edar Receptor ,Morphogenesis/genetics ,EDAR ,Edar Receptor/genetics ,Latin America ,Phenotype ,Ear Auricle/anatomy & histology/embryology ,purl.org/pe-repo/ocde/ford#1.04.00 [https] ,genome-wide association ,Female ,T-Box Domain Proteins ,CIENCIAS NATURALES Y EXACTAS ,Ear Auricle ,Genome-Wide Association Study - Abstract
Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1., The shape of the pinna varies widely in the general human population but the genetic basis of this variation is unknown. Here Adhikari et al. conduct a genome-wide association study in Latin Americans and discover seven gene regions influencing pinna morphology, including EDAR and TBX15.
- Published
- 2015
16. Prediction of eye, hair and skin colour in Latin Americans
- Author
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Palmal, Sagnik, Adhikari, Kaustubh, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Silva de Cerqueira, Caio C., Bonfante, Betty, Chacón-Duque, Juan Camilo, Sohail, Anood, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo-Martínez, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Parolin, Maria-Laura, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Faux, Pierre, Ruiz-Linares, Andrés, Palmal, Sagnik, Adhikari, Kaustubh, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Silva de Cerqueira, Caio C., Bonfante, Betty, Chacón-Duque, Juan Camilo, Sohail, Anood, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo-Martínez, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Parolin, Maria-Laura, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Faux, Pierre, and Ruiz-Linares, Andrés
- Abstract
Here we evaluate the accuracy of prediction for eye, hair and skin pigmentation in a dataset of > 6,500 individuals from Mexico, Colombia, Peru, Chile and Brazil (including genome-wide SNP data and quantitative/categorical pigmentation phenotypes - the CANDELA dataset CAN). We evaluated accuracy in relation to different analytical methods and various phenotypic predictors. As expected from statistical principles, we observe that quantitative traits are more sensitive to changes in the prediction models than categorical traits. We find that Random Forest or Linear Regression are generally the best performing methods. We also compare the prediction accuracy of SNP sets defined in the CAN dataset (including 56, 101 and 120 SNPs for eye, hair and skin colour prediction, respectively) to the well-established HIrisPlex-S SNP set (including 6, 22 and 36 SNPs for eye, hair and skin colour prediction respectively). When training prediction models on the CAN data, we observe remarkably similar performances for HIrisPlex-S and the larger CAN SNP sets for the prediction of hair (categorical) and eye (both categorical and quantitative), while the CAN sets outperform HIrisPlex-S for quantitative, but not for categorical skin pigmentation prediction. The performance of HIrisPlex-S, when models are trained in a world-wide sample (although consisting of 80% Europeans, https://hirisplex.erasmusmc.nl), is lower relative to training in the CAN data (particularly for hair and skin colour). Altogether, our observations are consistent with common variation of eye and hair colour having a relatively simple genetic architecture, which is well captured by HIrisPlex-S, even in admixed Latin Americans (with partial European ancestry). By contrast, since skin pigmentation is a more polygenic trait, accuracy is more sensitive to prediction SNP set size, although here this effect was only apparent for a quantitative measure of skin pigmentation. Our results support the use of HIrisPlex-S in the p
17. A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation
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Bonfante, Betty, Faux, Pierre, Navarro, Nicolas, Mendoza-Revilla, Javier, Dubied, Morgane, Montillot, Charlotte, Wentworth, Emma, Poloni, Lauriane, Varón-González, Ceferino, Jones, Philip, Xiong, Ziyi, Fuentes-Guajardo, Macarena, Palmal, Sagnik, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Everardo-Martínez, Paola, Sánchez-Quinto, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Liu, Fan, Weinberg, Seth M., Shaffer, John R., Stergiakouli, Evie, Howe, Laurence J., Hysi, Pirro G., Spector, Timothy D., Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Thauvin-Robinet, Christel, Faivre, Laurence, Costedoat, Caroline, Balding, David, Cox, Timothy, Kayser, Manfred, Duplomb, Laurence, Yalcin, Binnaz, Cotney, Justin, Adhikari, Kaustubh, Ruiz-Linares, Andrés, Bonfante, Betty, Faux, Pierre, Navarro, Nicolas, Mendoza-Revilla, Javier, Dubied, Morgane, Montillot, Charlotte, Wentworth, Emma, Poloni, Lauriane, Varón-González, Ceferino, Jones, Philip, Xiong, Ziyi, Fuentes-Guajardo, Macarena, Palmal, Sagnik, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Everardo-Martínez, Paola, Sánchez-Quinto, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Liu, Fan, Weinberg, Seth M., Shaffer, John R., Stergiakouli, Evie, Howe, Laurence J., Hysi, Pirro G., Spector, Timothy D., Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Thauvin-Robinet, Christel, Faivre, Laurence, Costedoat, Caroline, Balding, David, Cox, Timothy, Kayser, Manfred, Duplomb, Laurence, Yalcin, Binnaz, Cotney, Justin, Adhikari, Kaustubh, and Ruiz-Linares, Andrés
- Abstract
To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.
18. A genome-wide association study identifies multiple loci for variation in human ear morphology
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Adhikari, Kaustubh, Reales, Guillermo, Smith, Andrew J. P., Konka, Esra, Palmen, Jutta, Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Fuentes, Macarena, Pizarro, María, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Calderón, Rosario, Rosique, Javier, Cheeseman, Michael, Bhutta, Mahmood F., Humphries, Steve E., Gonzalez-José, Rolando, Headon, Denis, Balding, David, Ruiz-Linares, Andrés, Adhikari, Kaustubh, Reales, Guillermo, Smith, Andrew J. P., Konka, Esra, Palmen, Jutta, Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Fuentes, Macarena, Pizarro, María, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Calderón, Rosario, Rosique, Javier, Cheeseman, Michael, Bhutta, Mahmood F., Humphries, Steve E., Gonzalez-José, Rolando, Headon, Denis, Balding, David, and Ruiz-Linares, Andrés
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Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.
19. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation
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Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Quinto-Sánchez, Mirsha, Mendoza-Revilla, Javier, Camilo Chacón-Duque, Juan, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Pérez, Gastón Macín, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Cheeseman, Michael, Rosique, Javier, Bedoya, Gabriel, Rothhammer, Francisco, Headon, Denis, González-José, Rolando, Balding, David, Ruiz-Linares, Andrés, Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Quinto-Sánchez, Mirsha, Mendoza-Revilla, Javier, Camilo Chacón-Duque, Juan, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Pérez, Gastón Macín, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Cheeseman, Michael, Rosique, Javier, Bedoya, Gabriel, Rothhammer, Francisco, Headon, Denis, González-José, Rolando, Balding, David, and Ruiz-Linares, Andrés
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We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar function.
20. Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance
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Chacón-Duque, Juan-Camilo, Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Mendoza-Revilla, Javier, Acuña-Alonzo, Victor, Barquera, Rodrigo, Quinto-Sánchez, Mirsha, Gómez-Valdés, Jorge, Everardo Martínez, Paola, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Villena, Mercedes, Vásquez, René, Llop, Elena, Sandoval, José R., Salazar-Granara, Alberto A., Parolin, Maria-Laura, Sandoval, Karla, Peñaloza-Espinosa, Rosenda I., Rangel-Villalobos, Hector, Winkler, Cheryl A., Klitz, William, Bravi, Claudio, Molina, Julio, Corach, Daniel, Barrantes, Ramiro, Gomes, Verónica, Resende, Carlos, Gusmão, Leonor, Amorim, Antonio, Xue, Yali, Dugoujon, Jean-Michel, Moral, Pedro, González-José, Rolando, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Poletti, Giovanni, Gallo, Carla, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Hellenthal, Garrett, Ruiz-Linares, Andrés, Chacón-Duque, Juan-Camilo, Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Mendoza-Revilla, Javier, Acuña-Alonzo, Victor, Barquera, Rodrigo, Quinto-Sánchez, Mirsha, Gómez-Valdés, Jorge, Everardo Martínez, Paola, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Villena, Mercedes, Vásquez, René, Llop, Elena, Sandoval, José R., Salazar-Granara, Alberto A., Parolin, Maria-Laura, Sandoval, Karla, Peñaloza-Espinosa, Rosenda I., Rangel-Villalobos, Hector, Winkler, Cheryl A., Klitz, William, Bravi, Claudio, Molina, Julio, Corach, Daniel, Barrantes, Ramiro, Gomes, Verónica, Resende, Carlos, Gusmão, Leonor, Amorim, Antonio, Xue, Yali, Dugoujon, Jean-Michel, Moral, Pedro, González-José, Rolando, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Poletti, Giovanni, Gallo, Carla, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Hellenthal, Garrett, and Ruiz-Linares, Andrés
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Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.
21. A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia
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Adhikari, Kaustubh, Mendoza-Revilla, Javier, Sohail, Anood, Fuentes-Guajardo, Macarena, Lampert, Jodie, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hunemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Salzano, Francisco M., Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Tobin, Desmond J., Fumagalli, Matteo, Balding, David, Ruiz-Linares, Andrés, Adhikari, Kaustubh, Mendoza-Revilla, Javier, Sohail, Anood, Fuentes-Guajardo, Macarena, Lampert, Jodie, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hunemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Salzano, Francisco M., Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Tobin, Desmond J., Fumagalli, Matteo, Balding, David, and Ruiz-Linares, Andrés
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We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
22. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features
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Adhikari, Kaustubh, Fontanil, Tania, Cal, Santiago, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Chacón-Duque, Juan-Camilo, Al-Saadi, Farah, Johansson, Jeanette A., Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Gonzalez-José, Rolando, Headon, Denis, López-Otín, Carlos, Tobin, Desmond J., Balding, David, Ruiz-Linares, Andrés, Adhikari, Kaustubh, Fontanil, Tania, Cal, Santiago, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Chacón-Duque, Juan-Camilo, Al-Saadi, Farah, Johansson, Jeanette A., Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Gonzalez-José, Rolando, Headon, Denis, López-Otín, Carlos, Tobin, Desmond J., Balding, David, and Ruiz-Linares, Andrés
- Abstract
We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.
23. Disentangling Signatures of Selection Before and After European Colonization in Latin Americans
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Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Fuentes-Guajardo, Macarena, Ormond, Louise, Wang, Ke, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Badillo Rivera, Keyla M., Nieves-Colón, Maria A., Gignoux, Christopher R., Wojcik, Genevieve L., Moreno-Estrada, Andrés, Hünemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Fumagalli, Matteo, Adhikari, Kaustubh, Ruiz-Linares, Andrés, Hellenthal, Garrett, Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Fuentes-Guajardo, Macarena, Ormond, Louise, Wang, Ke, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Badillo Rivera, Keyla M., Nieves-Colón, Maria A., Gignoux, Christopher R., Wojcik, Genevieve L., Moreno-Estrada, Andrés, Hünemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Fumagalli, Matteo, Adhikari, Kaustubh, Ruiz-Linares, Andrés, and Hellenthal, Garrett
- Abstract
Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
24. Neanderthal introgression in SCN9A impacts mechanical pain sensitivity
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Faux, Pierre, Ding, Li, Ramirez-Aristeguieta, Luis Miguel, Chacón-Duque, J. Camilo, Comini, Maddalena, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Jaramillo, Claudia, Arias, William, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Barquera, Rodrigo, Everardo-Martínez, Paola, Quinto-Sánchez, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Poletti, Giovanni, Gallo, Carla, Rothhammer, Francisco, Rojas, Winston, Schmid, Annina B., Adhikari, Kaustubh, Bennett, David L., Ruiz-Linares, Andrés, Faux, Pierre, Ding, Li, Ramirez-Aristeguieta, Luis Miguel, Chacón-Duque, J. Camilo, Comini, Maddalena, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Jaramillo, Claudia, Arias, William, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Barquera, Rodrigo, Everardo-Martínez, Paola, Quinto-Sánchez, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Poletti, Giovanni, Gallo, Carla, Rothhammer, Francisco, Rojas, Winston, Schmid, Annina B., Adhikari, Kaustubh, Bennett, David L., and Ruiz-Linares, Andrés
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The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function.
25. Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape
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Li, Qing, Chen, Jieyi, Faux, Pierre, Delgado, Miguel Eduardo, Bonfante, Betty, Fuentes-Guajardo, Macarena, Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Everardo-Martínez, Paola, Sánchez-Quinto, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Wu, Sijie, Du, Siyuan, Giardina, Andrea, Paria, Soumya Subhra, Khokan, Mahfuzur Rahman, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Rojas, Winston, Rothhammer, Francisco, Navarro, Nicolas, Wang, Sijia, Adhikari, Kaustubh, Ruiz-Linares, Andrés, Li, Qing, Chen, Jieyi, Faux, Pierre, Delgado, Miguel Eduardo, Bonfante, Betty, Fuentes-Guajardo, Macarena, Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Everardo-Martínez, Paola, Sánchez-Quinto, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Wu, Sijie, Du, Siyuan, Giardina, Andrea, Paria, Soumya Subhra, Khokan, Mahfuzur Rahman, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Rojas, Winston, Rothhammer, Francisco, Navarro, Nicolas, Wang, Sijia, Adhikari, Kaustubh, and Ruiz-Linares, Andrés
- Abstract
We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10−8) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features.
26. Disentangling Signatures of Selection Before and After European Colonization in Latin Americans
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Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Fuentes-Guajardo, Macarena, Ormond, Louise, Wang, Ke, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Badillo Rivera, Keyla M., Nieves-Colón, Maria A., Gignoux, Christopher R., Wojcik, Genevieve L., Moreno-Estrada, Andrés, Hünemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Fumagalli, Matteo, Adhikari, Kaustubh, Ruiz-Linares, Andrés, Hellenthal, Garrett, Mendoza-Revilla, Javier, Chacón-Duque, J. Camilo, Fuentes-Guajardo, Macarena, Ormond, Louise, Wang, Ke, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Badillo Rivera, Keyla M., Nieves-Colón, Maria A., Gignoux, Christopher R., Wojcik, Genevieve L., Moreno-Estrada, Andrés, Hünemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Fumagalli, Matteo, Adhikari, Kaustubh, Ruiz-Linares, Andrés, and Hellenthal, Garrett
- Abstract
Throughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. Although classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations, we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ∼4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico, and Peru. Our approach replicates previous reports of selection in the human leukocyte antigen region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
27. A genome-wide association study identifies multiple loci for variation in human ear morphology
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Adhikari, Kaustubh, Reales, Guillermo, Smith, Andrew J. P., Konka, Esra, Palmen, Jutta, Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Fuentes, Macarena, Pizarro, María, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Calderón, Rosario, Rosique, Javier, Cheeseman, Michael, Bhutta, Mahmood F., Humphries, Steve E., Gonzalez-José, Rolando, Headon, Denis, Balding, David, Ruiz-Linares, Andrés, Adhikari, Kaustubh, Reales, Guillermo, Smith, Andrew J. P., Konka, Esra, Palmen, Jutta, Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Fuentes, Macarena, Pizarro, María, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Calderón, Rosario, Rosique, Javier, Cheeseman, Michael, Bhutta, Mahmood F., Humphries, Steve E., Gonzalez-José, Rolando, Headon, Denis, Balding, David, and Ruiz-Linares, Andrés
- Abstract
Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1.
28. Prediction of eye, hair and skin colour in Latin Americans
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Palmal, Sagnik, Adhikari, Kaustubh, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Silva de Cerqueira, Caio C., Bonfante, Betty, Chacón-Duque, Juan Camilo, Sohail, Anood, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo-Martínez, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Parolin, Maria-Laura, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Faux, Pierre, Ruiz-Linares, Andrés, Palmal, Sagnik, Adhikari, Kaustubh, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Silva de Cerqueira, Caio C., Bonfante, Betty, Chacón-Duque, Juan Camilo, Sohail, Anood, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo-Martínez, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Parolin, Maria-Laura, Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Faux, Pierre, and Ruiz-Linares, Andrés
- Abstract
Here we evaluate the accuracy of prediction for eye, hair and skin pigmentation in a dataset of > 6,500 individuals from Mexico, Colombia, Peru, Chile and Brazil (including genome-wide SNP data and quantitative/categorical pigmentation phenotypes - the CANDELA dataset CAN). We evaluated accuracy in relation to different analytical methods and various phenotypic predictors. As expected from statistical principles, we observe that quantitative traits are more sensitive to changes in the prediction models than categorical traits. We find that Random Forest or Linear Regression are generally the best performing methods. We also compare the prediction accuracy of SNP sets defined in the CAN dataset (including 56, 101 and 120 SNPs for eye, hair and skin colour prediction, respectively) to the well-established HIrisPlex-S SNP set (including 6, 22 and 36 SNPs for eye, hair and skin colour prediction respectively). When training prediction models on the CAN data, we observe remarkably similar performances for HIrisPlex-S and the larger CAN SNP sets for the prediction of hair (categorical) and eye (both categorical and quantitative), while the CAN sets outperform HIrisPlex-S for quantitative, but not for categorical skin pigmentation prediction. The performance of HIrisPlex-S, when models are trained in a world-wide sample (although consisting of 80% Europeans, https://hirisplex.erasmusmc.nl), is lower relative to training in the CAN data (particularly for hair and skin colour). Altogether, our observations are consistent with common variation of eye and hair colour having a relatively simple genetic architecture, which is well captured by HIrisPlex-S, even in admixed Latin Americans (with partial European ancestry). By contrast, since skin pigmentation is a more polygenic trait, accuracy is more sensitive to prediction SNP set size, although here this effect was only apparent for a quantitative measure of skin pigmentation. Our results support the use of HIrisPlex-S in the p
29. A GWAS in Latin Americans identifies novel face shape loci, implicating VPS13B and a Denisovan introgressed region in facial variation
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Bonfante, Betty, Faux, Pierre, Navarro, Nicolas, Mendoza-Revilla, Javier, Dubied, Morgane, Montillot, Charlotte, Wentworth, Emma, Poloni, Lauriane, Varón-González, Ceferino, Jones, Philip, Xiong, Ziyi, Fuentes-Guajardo, Macarena, Palmal, Sagnik, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Everardo-Martínez, Paola, Sánchez-Quinto, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Liu, Fan, Weinberg, Seth M., Shaffer, John R., Stergiakouli, Evie, Howe, Laurence J., Hysi, Pirro G., Spector, Timothy D., Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Thauvin-Robinet, Christel, Faivre, Laurence, Costedoat, Caroline, Balding, David, Cox, Timothy, Kayser, Manfred, Duplomb, Laurence, Yalcin, Binnaz, Cotney, Justin, Adhikari, Kaustubh, Ruiz-Linares, Andrés, Bonfante, Betty, Faux, Pierre, Navarro, Nicolas, Mendoza-Revilla, Javier, Dubied, Morgane, Montillot, Charlotte, Wentworth, Emma, Poloni, Lauriane, Varón-González, Ceferino, Jones, Philip, Xiong, Ziyi, Fuentes-Guajardo, Macarena, Palmal, Sagnik, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Jaramillo, Claudia, Arias, William, Barquera, Rodrigo, Everardo-Martínez, Paola, Sánchez-Quinto, Mirsha, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hünemeier, Tábita, Ramallo, Virginia, Liu, Fan, Weinberg, Seth M., Shaffer, John R., Stergiakouli, Evie, Howe, Laurence J., Hysi, Pirro G., Spector, Timothy D., Gonzalez-José, Rolando, Schüler-Faccini, Lavinia, Bortolini, Maria-Cátira, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Thauvin-Robinet, Christel, Faivre, Laurence, Costedoat, Caroline, Balding, David, Cox, Timothy, Kayser, Manfred, Duplomb, Laurence, Yalcin, Binnaz, Cotney, Justin, Adhikari, Kaustubh, and Ruiz-Linares, Andrés
- Abstract
To characterize the genetic basis of facial features in Latin Americans, we performed a genome-wide association study (GWAS) of more than 6000 individuals using 59 landmark-based measurements from two-dimensional profile photographs and ~9,000,000 genotyped or imputed single-nucleotide polymorphisms. We detected significant association of 32 traits with at least 1 (and up to 6) of 32 different genomic regions, more than doubling the number of robustly associated face morphology loci reported until now (from 11 to 23). These GWAS hits are strongly enriched in regulatory sequences active specifically during craniofacial development. The associated region in 1p12 includes a tract of archaic adaptive introgression, with a Denisovan haplotype common in Native Americans affecting particularly lip thickness. Among the nine previously unidentified face morphology loci we identified is the VPS13B gene region, and we show that variants in this region also affect midfacial morphology in mice.
30. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation
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Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Quinto-Sánchez, Mirsha, Mendoza-Revilla, Javier, Camilo Chacón-Duque, Juan, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Pérez, Gastón Macín, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Cheeseman, Michael, Rosique, Javier, Bedoya, Gabriel, Rothhammer, Francisco, Headon, Denis, González-José, Rolando, Balding, David, Ruiz-Linares, Andrés, Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Quinto-Sánchez, Mirsha, Mendoza-Revilla, Javier, Camilo Chacón-Duque, Juan, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Pérez, Gastón Macín, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Cheeseman, Michael, Rosique, Javier, Bedoya, Gabriel, Rothhammer, Francisco, Headon, Denis, González-José, Rolando, Balding, David, and Ruiz-Linares, Andrés
- Abstract
We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar function.
31. Latin Americans show wide-spread Converso ancestry and imprint of local Native ancestry on physical appearance
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Chacón-Duque, Juan-Camilo, Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Mendoza-Revilla, Javier, Acuña-Alonzo, Victor, Barquera, Rodrigo, Quinto-Sánchez, Mirsha, Gómez-Valdés, Jorge, Everardo Martínez, Paola, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Villena, Mercedes, Vásquez, René, Llop, Elena, Sandoval, José R., Salazar-Granara, Alberto A., Parolin, Maria-Laura, Sandoval, Karla, Peñaloza-Espinosa, Rosenda I., Rangel-Villalobos, Hector, Winkler, Cheryl A., Klitz, William, Bravi, Claudio, Molina, Julio, Corach, Daniel, Barrantes, Ramiro, Gomes, Verónica, Resende, Carlos, Gusmão, Leonor, Amorim, Antonio, Xue, Yali, Dugoujon, Jean-Michel, Moral, Pedro, González-José, Rolando, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Poletti, Giovanni, Gallo, Carla, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Hellenthal, Garrett, Ruiz-Linares, Andrés, Chacón-Duque, Juan-Camilo, Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Mendoza-Revilla, Javier, Acuña-Alonzo, Victor, Barquera, Rodrigo, Quinto-Sánchez, Mirsha, Gómez-Valdés, Jorge, Everardo Martínez, Paola, Villamil-Ramírez, Hugo, Hünemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Villena, Mercedes, Vásquez, René, Llop, Elena, Sandoval, José R., Salazar-Granara, Alberto A., Parolin, Maria-Laura, Sandoval, Karla, Peñaloza-Espinosa, Rosenda I., Rangel-Villalobos, Hector, Winkler, Cheryl A., Klitz, William, Bravi, Claudio, Molina, Julio, Corach, Daniel, Barrantes, Ramiro, Gomes, Verónica, Resende, Carlos, Gusmão, Leonor, Amorim, Antonio, Xue, Yali, Dugoujon, Jean-Michel, Moral, Pedro, González-José, Rolando, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Poletti, Giovanni, Gallo, Carla, Bedoya, Gabriel, Rothhammer, Francisco, Balding, David, Hellenthal, Garrett, and Ruiz-Linares, Andrés
- Abstract
Historical records and genetic analyses indicate that Latin Americans trace their ancestry mainly to the intermixing (admixture) of Native Americans, Europeans and Sub-Saharan Africans. Using novel haplotype-based methods, here we infer sub-continental ancestry in over 6,500 Latin Americans and evaluate the impact of regional ancestry variation on physical appearance. We find that Native American ancestry components in Latin Americans correspond geographically to the present-day genetic structure of Native groups, and that sources of non-Native ancestry, and admixture timings, match documented migratory flows. We also detect South/East Mediterranean ancestry across Latin America, probably stemming mostly from the clandestine colonial migration of Christian converts of non-European origin (Conversos). Furthermore, we find that ancestry related to highland (Central Andean) versus lowland (Mapuche) Natives is associated with variation in facial features, particularly nose morphology, and detect significant differences in allele frequencies between these groups at loci previously associated with nose morphology in this sample.
32. A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia
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Adhikari, Kaustubh, Mendoza-Revilla, Javier, Sohail, Anood, Fuentes-Guajardo, Macarena, Lampert, Jodie, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo, Paola, Gómez-Valdés, Jorge, Adhikari, Kaustubh, Mendoza-Revilla, Javier, Sohail, Anood, Fuentes-Guajardo, Macarena, Lampert, Jodie, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo, Paola, and Gómez-Valdés, Jorge
- Abstract
We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans.
33. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features
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Adhikari, Kaustubh, Fontanil, Tania, Cal, Santiago, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Chacón-Duque, Juan-Camilo, Al-Saadi, Farah, Johansson, Jeanette A., Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Gonzalez-José, Rolando, Headon, Denis, López-Otín, Carlos, Tobin, Desmond J., Balding, David, Ruiz-Linares, Andrés, Adhikari, Kaustubh, Fontanil, Tania, Cal, Santiago, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Chacón-Duque, Juan-Camilo, Al-Saadi, Farah, Johansson, Jeanette A., Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Gonzalez-José, Rolando, Headon, Denis, López-Otín, Carlos, Tobin, Desmond J., Balding, David, and Ruiz-Linares, Andrés
- Abstract
We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.
34. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation.
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Adhikari K, Fuentes-Guajardo M, Quinto-Sánchez M, Mendoza-Revilla J, Camilo Chacón-Duque J, Acuña-Alonzo V, Jaramillo C, Arias W, Lozano RB, Pérez GM, Gómez-Valdés J, Villamil-Ramírez H, Hunemeier T, Ramallo V, Silva de Cerqueira CC, Hurtado M, Villegas V, Granja V, Gallo C, Poletti G, Schuler-Faccini L, Salzano FM, Bortolini MC, Canizales-Quinteros S, Cheeseman M, Rosique J, Bedoya G, Rothhammer F, Headon D, González-José R, Balding D, and Ruiz-Linares A
- Subjects
- Adult, Anatomic Variation, Animals, Genome-Wide Association Study, Humans, Latin America, Maxillofacial Development genetics, Mice, Polymorphism, Single Nucleotide, Young Adult, Cadherin Related Proteins genetics, Core Binding Factor Alpha 1 Subunit genetics, Edar Receptor genetics, Face anatomy & histology, Nerve Tissue Proteins genetics, Paired Box Transcription Factors genetics, Zinc Finger Protein Gli3 genetics
- Abstract
We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values<5 × 10(-8)) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar funtion.
- Published
- 2016
- Full Text
- View/download PDF
35. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features.
- Author
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Adhikari K, Fontanil T, Cal S, Mendoza-Revilla J, Fuentes-Guajardo M, Chacón-Duque JC, Al-Saadi F, Johansson JA, Quinto-Sanchez M, Acuña-Alonzo V, Jaramillo C, Arias W, Barquera Lozano R, Macín Pérez G, Gómez-Valdés J, Villamil-Ramírez H, Hunemeier T, Ramallo V, Silva de Cerqueira CC, Hurtado M, Villegas V, Granja V, Gallo C, Poletti G, Schuler-Faccini L, Salzano FM, Bortolini MC, Canizales-Quinteros S, Rothhammer F, Bedoya G, Gonzalez-José R, Headon D, López-Otín C, Tobin DJ, Balding D, and Ruiz-Linares A
- Subjects
- Female, Genetic Variation, Humans, Male, Face physiology, Gene Expression Regulation physiology, Genome-Wide Association Study, Hair growth & development, Racial Groups, Scalp physiology
- Abstract
We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10(-8) to 3 × 10(-119)), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair.
- Published
- 2016
- Full Text
- View/download PDF
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