(A) A single nucleotide polymorphism (SNP) is a frequent (>1%) genomic variant at a single base position in the DNA. Some SNPs in the coding region of a gene (exon) change the amino acid sequence of a protein, and others in the coding region do not affect the protein sequence.
(B) Polygenic risk scores (PRS) are typically calculated by summing the weighted allele counts of independent (i.e., uncorrelated) SNPs found to be associated with a trait or disorder in a genome-wide association study (GWAS). For quantitative traits, the weights are the linear regression effect sizes, i.e., the β coefficients. The weights for case/control phenotypes are the natural logarithm of the odds ratio, ln(OR).
(C ) Polygenic risk scores (PRS) follow a normal distribution on a population level. The distributions of cases and controls clearly overlap. Thus, meaningful risk predictions can be only expected for extreme quantiles at the top and bottom of the PRS distributions.
Related content
Major Depressive Disorder (MDD) is a highly prevalent psychiatric condition with significant individual and socio-economic burden. Despite the broad availability of numerous effective therapeutic interventions, up to 30% of patients fail to achieve adequate symptom relief and are classified as having treatment-resistant depression (TRD). TRD represents a significant clinical challenge, affecting approximately 30% of individuals with MDD who fail to respond to at least two adequate antidepressant trials.
Sequential treatment optimization scheme for major depressive disorder generated according to international evidence.
Key steps for managing factors that may confound antidepressant treatment response, including dose, side effects, comorbidities, stressors, adherence, pharmacogenomics, interactions, and treatment algorithms.