Postadmixture Selection on Chileans Targets Haplotype Involved in Pigmentation, Thermogenesis and Immune Defense against Pathogens
GENOME BIOLOGY AND EVOLUTION
Authors: Vicuna, Lucas; Klimenkova, Olga; Norambuena, Tomas; Martinez, Felipe, I; Fernandez, Mario, I; Shchur, Vladimir; Eyheramendy, Susana
Abstract
Detection of positive selection signatures in populations around the world is helping to uncover recent human evolutionary history as well as the genetic basis of diseases. Most human evolutionary genomic studies have been performed in European, African, and Asian populations. However, populations with Native American ancestry have been largely underrepresented. Here, we used a genome-wide local ancestry enrichment approach complemented with neutral simulations to identify postadmixture adaptations underwent by admixed Chileans through gene flow from Europeans into local Native Americans. The top significant hits (P=2.4x10(-7)) are variants in a region on chromosome 12 comprising multiple regulatory elements. This region includes rs12821256, which regulates the expression of KITLG, a well-known gene involved in lighter hair and skin pigmentation in Europeans as well as in thermogenesis. Another variant from that region is associated with the long noncoding RNA RP11-13A1.1, which has been specifically involved in the innate immune response against infectious pathogens. Our results suggest that these genes were relevant for adaptation in Chileans following the Columbian exchange.
Association between DNA methylation of the KITLG gene and cortisol levels under stress: a replication study
STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS
Authors: Wrigglesworth, Jo; Ancelin, Marie-Laure; Ritchie, Karen; Ryan, Joanne
Abstract
A recent study reported for the first time, that DNA methylation of the KITLG gene mediates the association between childhood trauma and cortisol stress reactivity. Our study aimed to provide the first independent replication of these findings. ESPRIT is a prospective study of community-dwelling participants (age >= 65), randomly selected from the electoral rolls of the Montpellier district, in France. Clinical depression was assessed using the Mini-International Neuropsychiatric Interview (MINI, French version 5.00), and the Centre for Epidemiological Studies Depression Scale (CES-D). Experiences of childhood adversity were ascertained via a 25-item questionnaire. Morning, evening, and diurnal salivary cortisol was measured under basal and stress conditions and determined using direct radioimmunoassay analysis. DNA methylation of the KITLG gene was quantified in whole blood using the SEQUENOM MassARRAY EpiTYPER platform. A significant negative association was observed between KITLG DNA methylation and both morning cortisol (beta = -1.846 +/- 0.666, p = .007) and diurnal cortisol (area under curve [AUC]) (beta = -19.429 +/- 8.868, p = .031) under a stress condition. However, only the former association was significant after correcting for multiple testing. Further, this association remained after adjusting for age, sex, and depression status. No significant association was observed between childhood trauma and KITLG DNA methylation in this older population. This study provides support for an association between KITLG methylation and stress cortisol levels, suggesting that DNA methylation of this gene may play a role in the longer term regulation of the stress system.Lay summary The significant negative association between KITLG DNA methylation and morning cortisol, measured under a stressful condition, suggests that individuals with higher KITLG methylation will secrete lower levels of cortisol whilst under stress.