Background: Current South American populations trace their origins mainly to three continental ancestries, i.e. European, Amerindian and African. Individual variation in relative proportions of each of these ancestries may be confounded with socioeconomic factors due to population stratification. Therefore, ancestry is a potential confounder variable that should be considered in epidemiologic studies and in public health plans. However, there are few studies that have assessed the ancestry of the current admixed Chilean population. This is partly due to the high cost of genome-scale technologies commonly used to estimate ancestry. In this study we have designed a small panel of SNPs to accurately assess ancestry in the largest sampling to date of the Chilean mestizo population (n = 3349) from eight cities. Our panel is also able to distinguish between the two main Amerindian components of Chileans: Aymara from the north and Mapuche from the south. Results: A panel of 150 ancestry-informative markers (AIMs) of SNP type was selected to maximize ancestry informativeness and genome coverage. Of these, 147 were successfully genotyped by KASPar assays in 2843 samples, with an average missing rate of 0.012, and a 0.95 concordance with microarray data. The ancestries estimated with the panel of AIMs had relative high correlations (0.88 for European, 0.91 for Amerindian, 0.70 for Aymara, and 0.68 for Mapuche components) with those obtained with AXIOM LAT1 array. The country's average ancestry was 0.53 ± 0.14 European, 0.04 ± 0.04 African, and 0.42 ± 0.14 Amerindian, disaggregated into 0.18 ± 0.15 Aymara and 0.25 ± 0.13 Mapuche. However, Mapuche ancestry was highest in the south (40.03%) and Aymara in the north (35.61%) as expected from the historical location of these ethnic groups. We make our results available through an online app and demonstrate how it can be used to adjust for ancestry when testing association between incidence of a disease and nongenetic risk factors.

BackgroundIncreased cortisol levels and genetic polymorphisms have been related to both major depressive disorder and antidepressant treatment outcome. The aim of this study is to evaluate the relationship between circadian salivary cortisol levels, cortisol suppression by dexamethasone and genetic polymorphisms in some HPA axis-related genes to the response to placebo and fluoxetine in depressed patients.MethodsThe diagnosis and severity of depression were performed using the Mini International Neuropsychiatric Interview (M.I.N.I.) and Hamilton depression scale (HAM-D17), respectively. Euthyroid patients were treated with placebo (one week) followed by fluoxetine (20 mg) (two months). Severity of depression was re-evaluated after placebo, three weeks and two months of fluoxetine treatments. Placebo response was defined as HAM-D17 score reductions of at least 25% and to < 15. Early response and response were reductions of at least 50% after three weeks and two months, and remission with ≤ 7 after two months. Plasma TSH, free-T4, circadian salivary cortisol levels and cortisol suppression by dexamethasone were evaluated. Seven genetic polymorphisms located in the Corticotrophin-releasing-hormone-receptor-1 (rs242939, rs242941, rs1876828), Corticotrophin-releasing-hormone-receptor-2 (rs2270007), Glucocorticoid-receptor (rs41423247), FK506-binding-protein-5 (rs1360780), and Arginine-vasopressin (rs3729965) genes were determined. Association analyses between response to placebo/fluoxetine and polymorphism were performed by chi-square or Fisher exact test. Cortisol levels were compared by t-test, ANOVA and the general linear model for repeated measures.Results208 depressed patients were recruited, 187 of whom were euthyroid. Placebo responders, fluoxetine responders and remitters exhibited significantly lower circadian cortisol levels than those who did not respond (p-values of 0.014, 0.008 and 0.021 respectively). Patients who abandoned treatment before the third week also exhibited a trend to low cortisol levels (p = 0.057). The polymorphisms rs242939 (CRHR1) and rs2270007 (CRHR2) were not in Hardy-Weinberg equilibrium. Only the rs242939 polymorphism (CRHR1) exhibited association with early response (three weeks) to fluoxetine (p-value = 0.043). No other association between outcomes and polymorphisms was observed.ConclusionsThese results support the clinical relevance of low salivary cortisol levels as a predictor of antidepressant response, either to placebo or to fluoxetine. Only one polymorphism in the CRHR1 gene was associated with the early response. Other factors may be involved in antidepressant response, although further studies are needed to identify them.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-014-0220-0) contains supplementary material, which is available to authorized users.

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Major depressive disorder is a serious mental disorder with high prevalence and recurrence rate. Once depression is diagnosed, effective pharmacological treatments must be rapidly initiated. Depression etiology and responsiveness to antidepressants have been related to the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Depressed subjects do not respond equally to the same drug. This variability could be explained by interindividual genetic differences related to HPA axis, including CRHR1 receptor.Objectives:To associate the salivary cortisol levels, prior to antidepressant treatment, and the CRHR1 rs242939 polymorphism with the response to therapy with fluoxetine.Methods:We performed a pharmacogenetic prospective longitudinal study including clinic follow-up, endocrine and genetic evaluations. After diagnosis, patients started the pharmacotherapy. the severity of the disease and clinical response were evaluated by the Hamilton Depression Rating Scale (HAM-D). Rapid and slow responses were considered as reductions in the HAM-D scores of at least 50% at the third and eight weeks respectively.Results:157 patients were recruited. Salivary cortisol levels at 8:00AM were lower in rapid responders than in not responders (p-value = 0.0122). No differences were observed after eight weeks of treatment. the rs242939 polymorphism was in Hardy Weinberg equilibrium (p = 0,24) and was significantly associated with early response (p = 0.019). there was no association after two month of therapy.Discussion and conclusions:Alterations in the CRHR1 receptor may significantly impact the regulation of stress response. the association observed in this study may be related with some refractoriness in the regulation of CRHR1 gene in non responders.Supported:By Fondecyt 1090219.