TY - JOUR
T1 - Neanderthal introgression in SCN9A impacts mechanical pain sensitivity
AU - Faux, Pierre
AU - Ding, Li
AU - Ramirez-Aristeguieta, Luis Miguel
AU - Chacón-Duque, J. Camilo
AU - Comini, Maddalena
AU - Mendoza-Revilla, Javier
AU - Fuentes-Guajardo, Macarena
AU - Jaramillo, Claudia
AU - Arias, William
AU - Hurtado, Malena
AU - Villegas, Valeria
AU - Granja, Vanessa
AU - Barquera, Rodrigo
AU - Everardo-Martínez, Paola
AU - Quinto-Sánchez, Mirsha
AU - Gómez-Valdés, Jorge
AU - Villamil-Ramírez, Hugo
AU - Silva de Cerqueira, Caio C.
AU - Hünemeier, Tábita
AU - Ramallo, Virginia
AU - Gonzalez-José, Rolando
AU - Schüler-Faccini, Lavinia
AU - Bortolini, Maria Cátira
AU - Acuña-Alonzo, Victor
AU - Canizales-Quinteros, Samuel
AU - Poletti, Giovanni
AU - Gallo, Carla
AU - Rothhammer, Francisco
AU - Rojas, Winston
AU - Schmid, Annina B.
AU - Adhikari, Kaustubh
AU - Bennett, David L.
AU - Ruiz-Linares, Andrés
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85173700008
U2 - 10.1038/s42003-023-05286-z
DO - 10.1038/s42003-023-05286-z
M3 - Article
C2 - 37816865
AN - SCOPUS:85173700008
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 958
ER -