2023-09-15
070_ Polygenic resilience scores for schizophrenia and childhood trauma in the psychosis continuum
Research Question and Aims
It is well known that often, people at elevated risk for a disorder never develop it. This has led to the investigation of plausible protective mechanisms in these individuals that would help them remain healthy despite their genetic burden and/or exposure to environmental risk factors. Recently, Hess et al. (2021) developed a “polygenic resilience score” for schizophrenia that captured the protective effect of common variation that would reduce the penetrance of risk variants for schizophrenia. Here, we aim to leverage this GWAS to calculate polygenic resilience scores for schizophrenia in healthy controls and patients with schizophrenia within the PsyCourse cohort to study i) how these polygenic resilience scores modulate the effect of polygenic risk for schizophrenia and environmental factors such as childhood trauma on the development of the disorder, and ii) whether they are associated with clinical and subclinical psychopathology, cognition and psychosocial functioning. Understanding how resilience variants keep us from developing a disorder could be a sound step toward finding more effective early interventions.
Analytic Plan
We hypothesize that individual genetic load for schizophrenia resilience influences the way genetic and environmental factors modulate the course and outcomes of schizophrenia.
Participants
Data from healthy controls and patients with schizophrenia within the PsyCourse cohort who have genotype data available will be included in this study.
Polygenic resilience scores
Polygenic risk scores (PRS) for schizophrenia resilience will be constructed based on the summary statistics of the latest genome-wide association studies (GWAS) for this trait. PRS-CS tool will be used to infer posterior SNP effect sizes under continuous shrinkage priors and estimate the global shrinkage parameter (φ) using a fully Bayesian approach. PRS will be then calculated in PLINK 1.9 using dosage data in this cohort.
Statistical analysis
Linear regressions will be used to examine the relationship between the different predictors and psychopathological, cognitive, and functioning outcomes.
Resources needed
v1_id
v1_stat
v1_center
gsa_id
Demographic information:
v1_sex
v1_age
v1_yob
v1_ed_status
Psychiatric history:
v1_cur_psy_trm
v1_outpat_psy_trm
v1_daypat_inpat_trm
v1_dur_illness
v1_1st_ep
v1_tms_daypat_outpat_trm
Medication:
v1_Antidepressants
v1_Antipsychotics
v1_Mood_stabilizers
v1_Tranquilizers
v1_Other_psychiatric
Family history of psychiatric illness:
v1_fam_hist
Substance abuse:
v1_can_cat_evr
DSM-IV Diagnosis:
v1_scid_dsm_dx_cat
v1_scid_ever_delus
v1_scid_ever_halls
v1_scid_ever_psyc
Symptom rating scales:
v1_panss_p1
v1_panss_p2
v1_panss_p3
v1_panss_p4
v1_panss_p5
v1_panss_p6
v1_panss_p7
v1_panss_n1
v1_panss_n2
v1_panss_n3
v1_panss_n4
v1_panss_n5
v1_panss_n6
v1_panss_n7
v1_panss_g1
v1_panss_g2
v1_panss_g3
v1_panss_g4
v1_panss_g5
v1_panss_g6
v1_panss_g7
v1_panss_g8
v1_panss_g9
v1_panss_g10
v1_panss_g11
v1_panss_g12
v1_panss_g13
v1_panss_g14
v1_panss_g15
v1_panss_g16
v1_panss_sum_pos
v1_panss_sum_neg
v1_panss_sum_gen
v1_panss_sum_tot
v1_idsc_sum
v1_ymrs_sum
v1_cgi_s
v1_gaf
Neuropsychology (cognitive tests):
v1_nrpsy_tmt_A_rt
v1_nrpsy_tmt_A_err
v1_nrpsy_tmt_B_rt
v1_nrpsy_tmt_B_err
v1_nrpsy_dgt_sp_frw
v1_nrpsy_dgt_sp_bck
v1_nrpsy_dg_sym
v1_nrpsy_mwtb
Questionnaires:
v1_cape_itm1A
v1_cape_itm1B
v1_cape_itm2A
v1_cape_itm2B
v1_cape_itm3A
v1_cape_itm3B
v1_cape_itm4A
v1_cape_itm4B
v1_cape_itm5A
v1_cape_itm5B
v1_cape_itm6A
v1_cape_itm6B
v1_cape_itm7A
v1_cape_itm7B
v1_cape_itm8A
v1_cape_itm8B
v1_cape_itm9A
v1_cape_itm9B
v1_cape_itm10A
v1_cape_itm10B
v1_cape_itm11A
v1_cape_itm11B
v1_cape_itm12A
v1_cape_itm12B
v1_cape_itm13A
v1_cape_itm13B
v1_cape_itm14A
v1_cape_itm14B
v1_cape_itm15A
v1_cape_itm15B
v1_cape_itm16A
v1_cape_itm16B
v1_cape_itm17A
v1_cape_itm17B
v1_cape_itm18A
v1_cape_itm18B
v1_cape_itm19A
v1_cape_itm19B
v1_cape_itm20A
v1_cape_itm20B
v1_cape_itm21A
v1_cape_itm21B
v1_cape_itm22A
v1_cape_itm22B
v1_cape_itm23A
v1_cape_itm23B
v1_cape_itm24A
v1_cape_itm24B
v1_cape_itm25A
v1_cape_itm25B
v1_cape_itm26A
v1_cape_itm26B
v1_cape_itm27A
v1_cape_itm27B
v1_cape_itm28A
v1_cape_itm28B
v1_cape_itm29A
v1_cape_itm29B
v1_cape_itm30A
v1_cape_itm30B
v1_cape_itm31A
v1_cape_itm31B
v1_cape_itm32A
v1_cape_itm32B
v1_cape_itm33A
v1_cape_itm33B
v1_cape_itm34A
v1_cape_itm34B
v1_cape_itm35A
v1_cape_itm35B
v1_cape_itm36A
v1_cape_itm36B
v1_cape_itm37A
v1_cape_itm37B
v1_cape_itm38A
v1_cape_itm38B
v1_cape_itm39A
v1_cape_itm39B
v1_cape_itm40A
v1_cape_itm40B
v1_cape_itm41A
v1_cape_itm41B
v1_cape_itm42A
v1_cape_itm42B
v1_bdi2_sum
v1_asrm_sum
v1_mss_sum
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
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
Assessment of disease course:
v4_opcrit
Genetic data:
Raw GSA genotypes to calculate PCAs
Imputed GSA genotypes for the calculation of PRS