2021-07-06

045_ Analysis of the interaction of PRS with childhood trauma and life events and its role in clinical outcomes in the PsyCourse dataset

Research Question and Aims

It is well-established that genetic and environmental factors play an important role in the development of severe mental illness (SMI) such as SCZ, BD, MDD and drug abuse. However, it is still unclear, to what extent gene-environment-interactions (GxE) in patients with SMI contribute to several outcomes. Therefore, the aim of the proposed project is to investigate whether GxE is an independent significant factor for drug use and clinical severity in patients with SMI. To estimate the genetic risk for SMI, we will use polygenic risk score (PRS) for several psychiatric traits. In addition, in our study we will consider those environmental factors related to traumatic events both in childhood and adulthood as well as other life events. Those can be quantified by using the questionnaires like the Childhood Trauma Questionnaire (CTQ) and the Life Events Questionnaire (LEQ).

Analytic Plan

The analysis will use the PsyCourse samples genotyped using the Global Screening Array (GSA). Using imputed data, polygenic risk scores for SCZ, BD, MDD, Educational Attainment and probably others based on upcoming GWASes of interest will be calculated in these subjects.
The potential effect of the interaction of PRS with Environmental factors (Childhood Trauma/Life Events) on several cross-sectional outcomes: drug use (use/not use, frequency of use) and clinical severity (as measured by psychopathological scales of positive/negative/manic/depressive symptoms) in psychiatric patients will be statistically assessed using linear/logistic models. These models will include covariates as well: age, sex, duration of disease, and ancestry components, among others. The relevance of the covariates for each model will be assessed using the AIC criteria.

Resources needed

Raw and imputed GSA data in PsyCourse subjects.

Clinical & Phenotypic data:
v1_sex
v1_age
v1_scid_dsm_dx_cat
v1_dur_illness
v1_age_1st_out_trm
v1_age_1st_inpat_trm
v1_cur_psy_trm
v1_panss_sum_pos
v1_panss_sum_neg
v1_panss_sum_gen
v1_ymrs_sum
v1_idsc_sum
v1_bdi2_sum
v1_asrm_sum
v1_idsc_sum
v1_mss_sum

v3_cts_1
v3_cts_2
v3_cts_3
v3_cts_4
v3_cts_5
v3_cts_els_dic
v3_cts_1_dic
v3_cts_2_dic
v3_cts_3_dic
v3_cts_4_dic
v3_cts_5_dic

v1_leq_A_1A
v1_leq_A_1B
v1_leq_A_2A
v1_leq_A_2B
v1_leq_A_3A
v1_leq_A_3B
v1_leq_A_4A
v1_leq_A_4B
v1_leq_A_5A
v1_leq_A_5B
v1_leq_A_6A
v1_leq_A_6B
v1_leq_A_7A
v1_leq_A_7B
v1_leq_A_8A
v1_leq_A_8B
v1_leq_A_9A
v1_leq_A_9B
v1_leq_B_10A
v1_leq_B_10B
v1_leq_B_11A
v1_leq_B_11B
v1_leq_B_12A
v1_leq_B_12B
v1_leq_B_13A
v1_leq_B_13B
v1_leq_B_14A
v1_leq_B_14B
v1_leq_B_15A
v1_leq_B_15B
v1_leq_B_16A
v1_leq_B_16B
v1_leq_B_17A
v1_leq_B_17B
v1_leq_B_18A
v1_leq_B_18B
v1_leq_B_19A
v1_leq_B_19B
v1_leq_C_20A
v1_leq_C_20B
v1_leq_C_21A
v1_leq_C_21B
v1_leq_C_22A
v1_leq_C_22B
v1_leq_C_23A
v1_leq_C_23B
v1_leq_D_24A
v1_leq_D_24B
v1_leq_D_25A
v1_leq_D_25B
v1_leq_D_26A
v1_leq_D_26B
v1_leq_D_27A
v1_leq_D_27B
v1_leq_E_28A
v1_leq_E_28B
v1_leq_E_29A
v1_leq_E_29B
v1_leq_E_30A
v1_leq_E_30B
v1_leq_E_31A
v1_leq_E_31B
v1_leq_E_32A
v1_leq_E_32B
v1_leq_E_33A
v1_leq_E_33B
v1_leq_E_34A
v1_leq_E_34B
v1_leq_E_35A
v1_leq_E_35B
v1_leq_E_36A
v1_leq_E_36B
v1_leq_E_37A
v1_leq_E_37B
v1_leq_E_38A
v1_leq_E_38B
v1_leq_E_39A
v1_leq_E_39B
v1_leq_E_40A
v1_leq_E_40B
v1_leq_E_41A
v1_leq_E_41B
v1_leq_E_42A
v1_leq_E_42B
v1_leq_F_43A
v1_leq_F_43B
v1_leq_F_44A
v1_leq_F_44B
v1_leq_F_45A
v1_leq_F_45B
v1_leq_F_46A
v1_leq_F_46B
v1_leq_F_47A
v1_leq_F_47B
v1_leq_F_48A
v1_leq_F_48B
v1_leq_F_49A
v1_leq_F_49B
v1_leq_F_50A
v1_leq_F_50B
v1_leq_G_51A
v1_leq_G_51B
v1_leq_G_52A
v1_leq_G_52B
v1_leq_G_53A
v1_leq_G_53B
v1_leq_G_54A
v1_leq_G_54B
v1_leq_G_55A
v1_leq_G_55B
v1_leq_H_56A
v1_leq_H_56B
v1_leq_H_57A
v1_leq_H_57B
v1_leq_H_58A
v1_leq_H_58B
v1_leq_H_59A
v1_leq_H_59B
v1_leq_H_60A
v1_leq_H_60B
v1_leq_H_61A
v1_leq_H_61B
v1_leq_H_62A
v1_leq_H_62B
v1_leq_H_63A
v1_leq_H_63B
v1_leq_H_64A
v1_leq_H_64B
v1_leq_H_65A
v1_leq_H_65B
v1_leq_H_66A
v1_leq_H_66B
v1_leq_H_67A
v1_leq_H_67B
v1_leq_H_68A
v1_leq_H_68B
v1_leq_I_69A
v1_leq_I_69B
v1_leq_I_70A
v1_leq_I_70B
v1_leq_I_71A
v1_leq_I_71B
v1_leq_I_72A
v1_leq_I_72B
v1_leq_I_73A
v1_leq_I_73B
v1_leq_J_74A
v1_leq_J_74B
v1_leq_J_75A
v1_leq_J_75B
v1_leq_J_76A
v1_leq_J_76B
v1_leq_J_77A
v1_leq_J_77B
v1_leq_J_78A
v1_leq_J_78B
v1_leq_J_79A
v1_leq_J_79B

v1_whoqol_itm1
v1_whoqol_itm2
v1_whoqol_itm3
v1_whoqol_itm4
v1_whoqol_itm5
v1_whoqol_itm6
v1_whoqol_itm7
v1_whoqol_itm8
v1_whoqol_itm9
v1_whoqol_itm10
v1_whoqol_itm11
v1_whoqol_itm12
v1_whoqol_itm13
v1_whoqol_itm14
v1_whoqol_itm15
v1_whoqol_itm16
v1_whoqol_itm17
v1_whoqol_itm18
v1_whoqol_itm19
v1_whoqol_itm20
v1_whoqol_itm21
v1_whoqol_itm22
v1_whoqol_itm23
v1_whoqol_itm24
v1_whoqol_itm25
v1_whoqol_itm26

Alcohol and smoking:
v1_ever_smkd
v1_age_smk
v1_no_cig

v1_alc_pst12_mths
v1_alc_5orm
v1_lftm_alc_dep

Raw data on medication and drug use
200715_v4.1_psycourse_clin_raw_med_(visit1 to visit4).RData
200715_v4.1_psycourse_clin_raw_ill_drg_(visit1 to visit4).RData