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Genetic Risk Scores

Genetic Risk Scores. Chelsea Thomas & Haley McPeek. What is a Genetic Risk Score?.

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Genetic Risk Scores

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  1. Genetic Risk Scores Chelsea Thomas & Haley McPeek

  2. What is a Genetic Risk Score? • A genetic risk score (GRS) is “a kind of summary of genetic risk from all the different variants in the genome that GWAS (genome wide association studies) had identified as predisposing” a certain disease or disorder. • They are multi-locus profiles of genetic risk based on genotypes at multiple single nucleotide polymorphisms (SNPs). Certain loci are known to be genetic risks for developing a disease (like schizophrenia), and the GRS is what measures these risks.

  3. GWAS & SNPs • A Genome Wide Association Study is a method where genomes are rapidly scanned across many people in order to find genetic variations associated with a particular disease. They are then put into a database to be compared with other’s DNA. • SNPs are simply these different genetic variations. If a SNP is located within a gene, it may play a more direct role in disease by affecting that gene’s function.

  4. Schizophrenia Gene DatabaseSZGene • The table lists all genetic loci with at least one nominally significant meta-analysis result in SZGene. Loci are ranked by statistical significance (P-value). • A grade "A" is assigned when the total number of minor alleles of cases and controls combined in the meta-analyses exceeds 1,000, "B" when it is between 100 and 1,000, and "C" when it is less than 100.

  5. Calculating GRS • SNPs that have been correlated with a certain disease (like schizophrenia, for example) are selected. • The number of risk alleles are also selected. • Using a complicated formula, these two factors are what go into computing a GRS:

  6. Understanding what different genetic risk scores mean • In order for us to understand what different GRS scores mean, we can look at two pretend patients. • Patient 1: AA, GG, TT, CT, AG, TT, GG / Patient 2: GG, GG, TT, TT, GC, CC, GC • This Researcher has made an online calculator where patients and doctors can use 7 genetic markers to determine their GRS for IgA Nephropathy (a biomarker for kidney disorders). • http://www.columbiamedicine.org/divisions/gharavi/calc_genetic.php

  7. Applying it to schizophrenia

  8. Applying it to schizophrenia (cont.) • GRS in today’s reading was used by calculating a GRS for each participant based on 41 SNPs. They were examining GRS and working memory. • They found that GRS did not correlate with age, SIRP performance, parental SES, or IQ. • There were no significant correlations between GRS and cumulative and current drug doses, nor negative/positive symptoms. • Score didn’t differ between gender, diagnostic group, or race.

  9. What does it mean? • GRS for schizophrenia positively correlated with increased working memory (WM)-related DLPFC activity. • However, GRS could not be correlated with symptom severity, population stratification, or group difference in WM performance. • Researchers concluded based on the fact that GRS was linked only to brain function and not performance/symptom severity that GRS reflects different genetic aspects that aren’t well represented in the clinical/cognitive performances of patients.

  10. http://sites.duke.edu/danbelsky/tag/genetic-risk-score/ • http://cran.r-project.org/web/packages/gtx/vignettes/ashg2012.pdf • http://ghr.nlm.nih.gov/handbook/genomicresearch/snp • http://web.archive.org/web/20110909085812/http://www.szgene.org/TopResults.asp

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