2 results
The use of Polygenic Scores in a family design of First Episode Psychosis
- N. Murillo-Garcia, S. Papiol, S. Barrio-Martínez, M. Sevilla-Ramos, R. Magdaleno-Herrero, Á. Yorca-Ruiz, V. Ortíz-García de la Foz, M. Miguel-Corredera, M. Fatjó-Vilas, R. Ayesa-Arriola
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S631
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
A wide variety of traits is heritable and has genetic loading, including schizophrenia spectrum disorders (SSDs) and its associated neurocognitive features. The genetic architecture of SSDs is polygenic, with the contribution of thousands of single nucleotide polymorphisms of small effect with an estimated SNP-heritability of 24%. The same occurs with neurocognitive phenotypes such as intelligence or educational attainment. Therefore, the method of polygenic risk scores (PRS) is useful in estimating the genetic burden of such traits. Moreover, the use of PRS in a sample of genetically related individuals would allow analyzing the contribution of genetic and environmental factors involved in the development of the disorder and its candidate endophenotypes.
ObjectivesTo estimate PRS for schizophrenia, and polygenic scores for intelligence and educational attainment in patients with First Episode Psychosis (FEP), their first-degree relatives (siblings and parents), and a group of healthy controls.
MethodsThe sample is comprised of 579 participants of the PAFIP-FAMILIAS project in Santander, Spain (133 FEP patients, their 244 first-degree relatives, and 202 healthy controls). All provided sociodemographic information and completed the same neuropsychological battery. Participants’ DNA was extracted from venous blood samples, and genotyping was performed at the Centro Nacional de Investigaciones Oncológicas (CeGen) by the Global Screening Array v.3.0 panel (Illumina). Data quality control, imputation, calculation of PRS, and genetic association analysis are being performed using PLINK, SHAPEIT, IMPUTE2, SPSS and R.
ResultsData analysis is currently in progress, at the quality analysis stage, in collaboration with the Institute of Psychiatric Phenomics and Genomics (IPPG) in Munich, Germany. We expect to find higher PRS for schizophrenia in FEP patients, while their first-degree relatives will potentially show intermediate risk scores between patients and healthy controls. A similar finding is expected regarding intelligence and educational attainment, as FEP patients may show more genetic burden for low intelligence and education.
ConclusionsThe estimation of PRS has demonstrated to be valuable in studying complex traits such as schizophrenia. We believe that by applying this method in a family design can provide interesting insights on the development of SSDs and its potential endophenotypes, and potentially useful in their prevention.
Disclosure of InterestNone Declared
Biomarkers as Proxies for Cognitive Reserve: the role of high density lipoprotein cholesterol in first episode of psychosis
- R. Magdaleno Herrero, N. Murillo-García, Á. Yorca-Ruiz, K. Neergaard, B. Crespo-Facorro, R. Ayesa-Arriola
-
- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S640
-
- Article
-
- You have access Access
- Open access
- Export citation
-
Introduction
The proxies used to compose cognitive reserve (CR) in first episode of psychosis (FEP) have varied in the literature. The development of FEP is linked to the peripheral pathways of the central nervous system (Leboyer et al. Psychopharmacology 2016; 233(9) 1651-60) Furthermore, schizophrenia has been linked to the metabolic system, indicating that alterations in the levels of biological parameters, in particular high-density lipoproteins (HDL) (Gjerde et al. Eur Arch Psychiatry Clin Neurosci 2020; 270(1) 49-58) cause worse global functioning and cognitive impairment (Adamowicz et al. J Clin Med 2020; 9(2) 537). Despite this knowledge, no research has considered the introduction of biomarkers as proxies for CR.
ObjectivesThe present study aimed to create a quantifiable and objective CR index that adjusts for the multifactorial nature of FEP.
MethodsWe included 668 patients who had FEP and 217 healthy controls who were assessed for sociodemographic information and levels of biological parameters: waist circumference, hypertension and levels of HDL, triglycerides and glucose. The main analyses were multiple regression analysis, principal component analysis (PCA) and exploratory factor analysis (EFA).
ResultsRegression analyses showed that HDL was the top performing biological parameter in a model containing years of education and unemployment (F=11.80; p<0.001) while also outperforming other parameters in a correlation analysis with a composite of the same variables (r= 0.21; p<0.001). In EFA analyses combining all possible components, we found that the most optimal proxies for the composition of biological CR were years of education and HDL. The results using PCA indicated that biological CR would have a greater explanatory power for the phenomenon than classical CR, increasing 7.27% of the explanation for FEP patients and 16.08% for healthy controls.
ConclusionsThis article proposes an objective and quantifiable method to measure CR, taking into account endogenous and exogenous factors. This index, introducing biomarkers as proxies could provide a more accurate CR score for FEP patients.
Disclosure of InterestNone Declared