Neanderthal introgression in SCN9A impacts mechanical pain sensitivity

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.

• Autores: Ramírez Aristeguieta, Luis Miguel; Jaramillo Alzate, Claudia Milena; Arias Pérez, William Hernán; Rojas Montoya, Winston; Bennett, David L.; Bortolini, Maria Cátira; Canizales Quinteros, Samuel; Chacón Duque, Juan Camilo; Comini, Maddalena; Ding, Li; Everardo Martínez, Paola; Faux, Pierre; Fuentes Guajardo, Macarena; Gallo, Carla; Gómez Valdés, Jorge; González José, Rolando; Granja, Vanessa; Hünemeier, Tábita; Hurtado, Malena; Acuña Alonzo, Victor; Mendoza Revilla, Javier; Poletti, Giovanni; Quinto Sánchez, Mirsha; Ramallo, Virginia; Adhikari, Kaustubh; Barquera, Rodrigo; Rothhammer, Francisco; Ruiz Linares, Andrés; Schüler Faccini, Lavinia; Silva de Cerqueira, Caio C.; Schmid, Annina B.; Villamil Ramírez, Hugo; Villegas, Valeria
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2023
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/43146
• Acceso en línea: https://hdl.handle.net/10495/43146
• Palabra clave: Canal de Sodio Activado por Voltaje NAV1.7 - genética; NAV1.7 Voltage-Gated Sodium Channel - genetics; Hombre de Neandertal - genética; Neanderthals - genetics; Nocicepción; Nociception; Dolor - genética; Pain - genetics; Umbral del Dolor; Pain Threshold; https://id.nlm.nih.gov/mesh/D062556; https://id.nlm.nih.gov/mesh/D059125; https://id.nlm.nih.gov/mesh/D059225; https://id.nlm.nih.gov/mesh/D010146; https://id.nlm.nih.gov/mesh/D017288
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/