Neanderthal introgression in SCN9A impacts mechanical pain sensitivity

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Fältnamn	Indikatorer	Metadata
000		04122naa a2200673 4500
001		oai:DiVA.org:su-225829
003		SwePub
008		240123s2023 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-2258292 URI
024	7	a https://doi.org/10.1038/s42003-023-05286-z2 DOI
040		a (SwePub)su
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Faux, Pierre4 aut
245	1 0	a Neanderthal introgression in SCN9A impacts mechanical pain sensitivity
264	1	c 2023
338		a print2 rdacarrier
520		a 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 similar to 123kb 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. Neanderthal-derived variants in the SCN9A gene (encoding the voltage gated sodium channel, Nav1.7) are associated with enhanced experimental mechanical pain sensitivity in modern humans.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
700	1	a Ding, Li4 aut
700	1	a Miguel Ramirez-Aristeguieta, Luis4 aut
700	1	a Chacón-Duque, J. Camilo,d 1988-u Stockholms universitet,Institutionen för arkeologi och antikens kultur,University College London, UK4 aut0 (Swepub:su)cach0137
700	1	a Comini, Maddalena4 aut
700	1	a Mendoza-Revilla, Javier4 aut
700	1	a Fuentes-Guajardo, Macarena4 aut
700	1	a Jaramillo, Claudia4 aut
700	1	a Arias, William4 aut
700	1	a Hurtado, Malena4 aut
700	1	a Villegas, Valeria4 aut
700	1	a Granja, Vanessa4 aut
700	1	a Barquera, Rodrigo4 aut
700	1	a Everardo-Martinez, Paola4 aut
700	1	a Quinto-Sanchez, Mirsha4 aut
700	1	a Gomez-Valdes, Jorge4 aut
700	1	a Villamil-Ramirez, Hugo4 aut
700	1	a Silva de Cerqueira, Caio C.4 aut
700	1	a Hunemeier, Tabita4 aut
700	1	a Ramallo, Virginia4 aut
700	1	a Gonzalez-Jose, Rolando4 aut
700	1	a Schuler-Faccini, Lavinia4 aut
700	1	a Bortolini, Maria-Catira4 aut
700	1	a Acuna-Alonzo, Victor4 aut
700	1	a Canizales-Quinteros, Samuel4 aut
700	1	a Poletti, Giovanni4 aut
700	1	a Gallo, Carla4 aut
700	1	a Rothhammer, Francisco4 aut
700	1	a Rojas, Winston4 aut
700	1	a Schmid, Annina B.4 aut
700	1	a Adhikari, Kaustubh4 aut
700	1	a Bennett, David L.4 aut
700	1	a Ruiz-Linares, Andres4 aut
710	2	a Stockholms universitetb Institutionen för arkeologi och antikens kultur4 org
773	0	t Communications Biologyg 6:1q 6:1x 2399-3642
856	4	u https://doi.org/10.1038/s42003-023-05286-zy Fulltext
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-225829
856	4 8	u https://doi.org/10.1038/s42003-023-05286-z

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