Communications Biology (Oct 2023)
Neanderthal introgression in SCN9A impacts mechanical pain sensitivity
- Pierre Faux,
- Li Ding,
- Luis Miguel Ramirez-Aristeguieta,
- J. Camilo Chacón-Duque,
- Maddalena Comini,
- Javier Mendoza-Revilla,
- Macarena Fuentes-Guajardo,
- Claudia Jaramillo,
- William Arias,
- Malena Hurtado,
- Valeria Villegas,
- Vanessa Granja,
- Rodrigo Barquera,
- Paola Everardo-Martínez,
- Mirsha Quinto-Sánchez,
- Jorge Gómez-Valdés,
- Hugo Villamil-Ramírez,
- Caio C. Silva de Cerqueira,
- Tábita Hünemeier,
- Virginia Ramallo,
- Rolando Gonzalez-José,
- Lavinia Schüler-Faccini,
- Maria-Cátira Bortolini,
- Victor Acuña-Alonzo,
- Samuel Canizales-Quinteros,
- Giovanni Poletti,
- Carla Gallo,
- Francisco Rothhammer,
- Winston Rojas,
- Annina B. Schmid,
- Kaustubh Adhikari,
- David L. Bennett,
- Andrés Ruiz-Linares
Affiliations
- Pierre Faux
- Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University
- Li Ding
- Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University
- Luis Miguel Ramirez-Aristeguieta
- QST Lab, Faculty of Odontology, Universidad de Antioquia
- J. Camilo Chacón-Duque
- Centre for Palaeogenetics
- Maddalena Comini
- Nuffield Department of Clinical Neurosciences, Oxford University
- Javier Mendoza-Revilla
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia
- Macarena Fuentes-Guajardo
- Departamento de Tecnología Médica, Facultad de Ciencias de la Salud, Universidad de Tarapacá
- Claudia Jaramillo
- GENMOL (Genética Molecular), Universidad de Antioquia
- William Arias
- GENMOL (Genética Molecular), Universidad de Antioquia
- Malena Hurtado
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia
- Valeria Villegas
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia
- Vanessa Granja
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia
- Rodrigo Barquera
- Molecular Genetics Laboratory, National School of Anthropology and History
- Paola Everardo-Martínez
- Molecular Genetics Laboratory, National School of Anthropology and History
- Mirsha Quinto-Sánchez
- Forensic Science, Faculty of Medicine, UNAM (Universidad Nacional Autónoma de México)
- Jorge Gómez-Valdés
- Molecular Genetics Laboratory, National School of Anthropology and History
- Hugo Villamil-Ramírez
- Unidad de Genomica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica
- Caio C. Silva de Cerqueira
- Scientific Police of São Paulo State
- Tábita Hünemeier
- Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo
- Virginia Ramallo
- Departamento de Genética, Universidade Federal do Rio Grande do Sul
- Rolando Gonzalez-José
- Instituto Patagónico de Ciencias Sociales y Humanas, Centro Nacional Patagónico, CONICET
- Lavinia Schüler-Faccini
- Departamento de Genética, Universidade Federal do Rio Grande do Sul
- Maria-Cátira Bortolini
- Departamento de Genética, Universidade Federal do Rio Grande do Sul
- Victor Acuña-Alonzo
- Molecular Genetics Laboratory, National School of Anthropology and History
- Samuel Canizales-Quinteros
- Unidad de Genomica de Poblaciones Aplicada a la Salud, Facultad de Química, UNAM-Instituto Nacional de Medicina Genómica
- Giovanni Poletti
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia
- Carla Gallo
- Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia
- Francisco Rothhammer
- Instituto de Alta Investigación, Universidad de Tarapacá, Arica
- Winston Rojas
- GENMOL (Genética Molecular), Universidad de Antioquia
- Annina B. Schmid
- Nuffield Department of Clinical Neurosciences, Oxford University
- Kaustubh Adhikari
- Department of Genetics, Evolution and Environment, University College London
- David L. Bennett
- Nuffield Department of Clinical Neurosciences, Oxford University
- Andrés Ruiz-Linares
- Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University
- DOI
- https://doi.org/10.1038/s42003-023-05286-z
- Journal volume & issue
-
Vol. 6,
no. 1
pp. 1 – 12
Abstract
Abstract 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.
