Evaluation of polygenic risk score performance and gene-environment interaction in an admixed Brazilian cohort

• Grant number: 18/09328-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 29, 2018
• End date: October 28, 2019
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Síntia Iole Nogueira Belangero
• Grantee: Marcos Leite Santoro
• Supervisor: Benjamin Neale
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Massachusetts General Hospital, United States
• Associated to the scholarship: 16/13737-0 - Polygenic score and transcriptomic analysis in children and teenagers at risk to psychiatric disorders, BP.PD

Abstract

This study aims to characterize the admixture of a longitudinal cohort of children and adolescents (Instituto Nacional da Psiquiatria do Desenvolvimento - INPD) and understand how ancestry influences the polygenic risk scores (PRS) of psychiatric disorders (PDs) in this cohort. Besides, we will simulate latin american genotypes in order to find which is the best reference panel to characterize this complex admixture accurately. Additionally, leveraging the longitudinal approach of INPD, we intend to which genotypes predispose the onset of major depressive disorder (MDD) and attention deficit hyperactivity disorder (ADHD). We will use Development and Well-Being Assessment (DAWBA) data to define the psychiatric diagnoses and other scales, applied to both parents and adolescents. Genotyping data is already available for 2240 individuals. We will use the available haplotypes from Simons Diversity Genome Project (SGDP) and the 1000 Genomes project as ancestral source data, appling (1) ADMIXTURE and RFMix to infer local ancestry, and (2) Admix-simu to simulate the latin american genotypes and to define which is the most accurate way to call ancestry for Latin American populations. PRS will be generated with Plink using the most up-to-date summary statistics from the Psychiatric Genomics Consortium genome-wide association studies. With this study, we hope to characterize the admixture of our sample and understand how this influences PRS, bem como entender quais são as melhores práticas para inferir ancestralidade local em populações miscigenadas. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ATKINSON, ELIZABETH G.; MAIHOFER, ADAM X.; KANAI, MASAHIRO; MARTIN, ALICIA R.; KARCZEWSKI, KONRAD J.; SANTORO, MARCOS L.; ULIRSCH, JACOB C.; KAMATANI, YOICHIRO; OKADA, YUKINORI; FINUCANE, HILARY K.; et al. Tractor uses local ancestry to enable the inclusion of admixed individuals in GWAS and to boost power. Nature Genetics, v. 53, n. 2, JAN 2021. (18/09328-2)

ATKINSON, ELIZABETH G.; MAIHOFER, ADAM X.; KANAI, MASAHIRO; MARTIN, ALICIA R.; KARCZEWSKI, KONRAD J.; SANTORO, MARCOS L.; ULIRSCH, JACOB C.; KAMATANI, YOICHIRO; OKADA, YUKINORI; FINUCANE, HILARY K.; et al. Tractor uses local ancestry to enable the inclusion of admixed individuals in GWAS and to boost power. Nature Genetics, v. 53, n. 2, p. 195+, FEB 2021. (18/09328-2)

ATKINSON, ELIZABETH G.; MAIHOFER, ADAM X.; KANAI, MASAHIRO; MARTIN, ALICIA R.; KARCZEWSKI, KONRAD J.; SANTORO, MARCOS L.; ULIRSCH, JACOB C.; KAMATANI, YOICHIRO; OKADA, YUKINORI; FINUCANE, HILARY K.; et al. Tractor uses local ancestry to enable the inclusion of admixed individuals in GWAS and to boost power. Nature Genetics, v. 53, n. 2, p. 21-pg., 2021-01-18. (18/09328-2)

ATKINSON, ELIZABETH; MAIHOFER, ADAM; KANAI, MASAHIRO; MARTIN, ALICIA; KARCZEWSKI, KONRAD; SANTORO, MARCOS; ULIRSCH, JACOB; KAMATANI, YOICHIRO; OKADA, YUKINORI; FINUCANE, HILARY; et al. Gene Discovery in Admixed Cohorts With Tractor. BIOLOGICAL PSYCHIATRY, v. 89, n. 9, p. 1-pg., 2021-05-01. (18/09328-2)