TY - JOUR
T1 - The genetic architecture of chronic mountain sickness in Peru
AU - Gazal, Steven
AU - Espinoza, Jose R.
AU - Austerlitz, Frédéric
AU - Marchant, Dominique
AU - Macarlupu, Jose Luis
AU - Rodriguez, Jorge
AU - Ju-Preciado, Hugo
AU - Rivera-Chira, Maria
AU - Hermine, Olivier
AU - Leon-Velarde, Fabiola
AU - Villafuerte, Francisco C.
AU - Richalet, Jean Paul
AU - Gouya, Laurent
N1 - Publisher Copyright:
Copyright © 2019 Gazal, Espinoza, Austerlitz, Marchant, Macarlupu, Rodriguez, Ju-Preciado, Rivera-Chira, Hermine, Leon-Velarde, Villafuerte, Richalet and Gouya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - Chronic mountain sickness (CMS)
KW - GWAS-genome-wide association study
KW - High altitude adaptation
KW - Monge's disease
KW - Natural selection
UR - https://www.scopus.com/pages/publications/85070583297
U2 - 10.3389/fgene.2019.00690
DO - 10.3389/fgene.2019.00690
M3 - Artículo
AN - SCOPUS:85070583297
SN - 1664-8021
VL - 10
JO - Frontiers in Genetics
JF - Frontiers in Genetics
IS - JUL
M1 - 690
ER -