The genetic architecture of chronic mountain sickness in Peru

Marchant, Dominique; León-Velarde, Fabiola; Richalet, Jean-Paul; Espinoza, Jose R.; Gouya, Laurent; Hermine, Olivier; Rivera Chira, Maria Concepcion; Macarlupu, Jose Luis; Ju-Preciado, Hugo; Rodriguez, Jorge; Gazal, Steven; Austerlitz, Frederic; Villafuerte, Francisco C.

dc.contributor.author	Gazal, Steven
dc.contributor.author	Espinoza, Jose R.
dc.contributor.author	Austerlitz, Frederic
dc.contributor.author	Marchant, Dominique
dc.contributor.author	Macarlupu, Jose Luis
dc.contributor.author	Rodriguez, Jorge
dc.contributor.author	Ju-Preciado, Hugo
dc.contributor.author	Rivera Chira, Maria Concepcion
dc.contributor.author	Hermine, Olivier
dc.contributor.author	León-Velarde, Fabiola
dc.contributor.author	Villafuerte, Francisco C.
dc.contributor.author	Richalet, Jean-Paul
dc.contributor.author	Gouya, Laurent
dc.date.accessioned	2019-12-06T20:57:51Z
dc.date.available	2019-12-06T20:57:51Z
dc.date.issued	2019
dc.identifier.uri	https://hdl.handle.net/20.500.12866/7451
dc.description.abstract	Chronic mountain sickness (CMS) is a pathological condition resulting from chronic exposure to high-altitude hypoxia. While its prevalence is high in native Andeans (>10%), little is known about the genetic architecture of this disease. Here, we performed the largest genome-wide association study (GWAS) of CMS (166 CMS patients and 146 controls living at 4,380 m in Peru) to detect genetic variants associated with CMS. We highlighted four new candidate loci, including the first CMS-associated variant reaching GWAS statistical significance (rs7304081; P = 4.58 × 10−9). By looking at differentially expressed genes between CMS patients and controls around these four loci, we suggested AEBP2, CAST, and MCTP2 as candidate CMS causal genes. None of the candidate loci were under strong natural selection, consistent with the observation that CMS affects fitness mainly after the reproductive years. Overall, our results reveal new insights on the genetic architecture of CMS and do not provide evidence that CMS-associated variants are linked to a strong ongoing adaptation to high altitude.	en_US
dc.language.iso	eng
dc.publisher	Frontiers Media
dc.relation.ispartofseries	Frontiers in Genetics
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject	adult	en_US
dc.subject	altitude disease	en_US
dc.subject	Article	en_US
dc.subject	chronic mountain sickness (CMS)	en_US
dc.subject	Chronic mountain sickness (CMS)	en_US
dc.subject	controlled study	en_US
dc.subject	DNA extraction	en_US
dc.subject	electrocardiography	en_US
dc.subject	female	en_US
dc.subject	forced expiratory volume	en_US
dc.subject	forced vital capacity	en_US
dc.subject	gene expression assay	en_US
dc.subject	gene frequency	en_US
dc.subject	gene locus	en_US
dc.subject	gene ontology	en_US
dc.subject	genetic architecture	en_US
dc.subject	genetic parameters	en_US
dc.subject	genetic variability	en_US
dc.subject	genome-wide association study	en_US
dc.subject	genotyping technique	en_US
dc.subject	GWAS-genome-wide association study	en_US
dc.subject	heart right ventricle hypertrophy	en_US
dc.subject	high altitude adaptation	en_US
dc.subject	High altitude adaptation	en_US
dc.subject	human	en_US
dc.subject	hypoxia inducible factor	en_US
dc.subject	major clinical study	en_US
dc.subject	male	en_US
dc.subject	middle aged	en_US
dc.subject	Monge's disease	en_US
dc.subject	multifactorial inheritance	en_US
dc.subject	natural selection	en_US
dc.subject	Natural selection	en_US
dc.subject	oximetry	en_US
dc.subject	oxygen saturation	en_US
dc.subject	Peru	en_US
dc.subject	population structure	en_US
dc.subject	quality control	en_US
dc.subject	quality of life	en_US
dc.subject	real time polymerase chain reaction	en_US
dc.subject	single nucleotide polymorphism	en_US
dc.subject	sphygmomanometry	en_US
dc.subject	spirometry	en_US
dc.title	The genetic architecture of chronic mountain sickness in Peru	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.3389/fgene.2019.00690
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#1.06.07
dc.relation.issn	1664-8021