2022-02-17

052_ Comorbidity analysis of schizophrenia patients using transcriptomic comorbid signatures

Research Question and Aims

In this study, we are investigating molecular mechanisms of comorbidity between schizophrenia and somatic diseases, such as type 2 diabetes and cardiovascular diseases. Using a large collection of publicly available transcriptomic datasets for these three disease classes, we have extracted transcriptomic signatures using non-negative matrix factorization (NMF). Using a reciprocal best-hit approach, we have reconstructed networks of disease signatures, identifying clusters in which several diseases are represented. We want to validate these comorbid signatures using the transcriptomic PsyCourse data combined to the relevant clinical variables associated to somatic risk factors, and validate that the comorbid signatures are associated with a higher risk for these diseases in the PsyCourse cohort.

Analytic Plan

1. Using the transcriptomic data from PsyCourse, we will apply NNLS to verify exposure of the patients to the comorbid signatures extracted from our training dataset
2. Association of the exposure to the comorbid signatures with relevant clinical variables which are predictive of disease risk for T2D and CVD will be verified. This will be performed using a multiple regression including covariates.
3. We will perform negative controls to verify that non-comorbid signatures are not/less associated to somatic risk factors.

Resources needed

OMICS dataset: RNA-seq transcriptomic on case samples (Raw dataset already available through Riya and preprocessing pipeline will be from ZI/Heidelberg)

Clinical/phenotypic variables
v1_sex
v1_age
v1_marital_stat
v1_partner
v1_no_bio_chld
v1_liv_aln
v1_school
v1_prof_dgr
v1_ed_status
v1_curr_paid_empl
v1_disabl_pens
v1_spec_emp
v1_wrk_abs_pst_5_yrs
v1_cur_work_restr
v1_height
v1_weight
v1_waist
v1_bmi
v1_chol_trig
v1_hyperten
v1_ang_pec
v1_heart_att
v1_stroke
v1_diabetes
v1_hyperthy
v1_hypothy
v1_osteopor
v1_asthma
v1_copd
v1_allerg
v1_neuroder
v1_psoriasis
v1_autoimm
v1_cancer
v1_stom_ulc
v1_kid_fail
v1_stone
v1_epilepsy
v1_migraine
v1_parkinson
v1_liv_cir_inf
v1_tbi
v1_beh
v1_eyear
v1_inf
v1_ever_smkd
v1_age_smk
v1_no_cig
v1_alc_pst12_mths
v1_lftm_alc_dep
v1_evr_ill_drg
v1_scid_dsm_dx
v1_scid_dsm_dx_cat
v1_scid_age_MDE
v1_scid_ever_delus
v1_scid_ever_halls
v1_scid_ever_psyc
v1_lexo_id
v2_lexo_id
v3_lexo_id
v4_lexo_id