Polygenic dissection of major depression clinical heterogeneity

摘要: The molecular mechanisms underlying major depressive disorder (MDD) are largely unknown. Limited success of previous genetics studies may be attributable to heterogeneity MDD, aggregating biologically different subtypes. We examined the polygenic features MDD and two common clinical subtypes (typical atypical) defined by symptom profiles in a large sample adults with established diagnoses. Data were from 1530 patients Netherlands Study Depression Anxiety (NESDA) 1700 controls mainly Twin Register (NTR). Diagnoses its based on DSM-IV symptoms. Genetic overlap psychiatric (MDD, bipolar disorder, schizophrenia) metabolic (body mass index (BMI), C-reactive protein, triglycerides) traits was evaluated via genomic profile risk scores (GPRS) generated meta-analysis results international consortia. Single nucleotide polymorphism (SNP)-heritability also estimated. associated GPRS, while no association found for GPRS traits. had differential signatures: typical strongly schizophrenia (odds ratio (OR)=1.54, P=7.8e-9), atypical additionally BMI (OR=1.29, P=2.7e-4) triglycerides (OR=1.21, P=0.006) GPRS. Similar when only highly discriminatory symptoms appetite/weight used define SNP-heritability 32% 38% 43% with, respectively, decreased (typical) increased (atypical) appetite/weight. In conclusion, characterized partially distinct liabilities represent more homogeneous phenotypes. Disentangling help field moving forward search roots depression.