Download Genetic Risk Scores

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Genetic Risk Scores
Chelsea Thomas & Haley McPeek
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What is a Genetic Risk Score?
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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.
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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.
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GWAS & SNPs
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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.
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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.
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Schizophrenia Gene Database
SZGene
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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).
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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.
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Calculating GRS
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SNPs that have been correlated with a certain disease (like
schizophrenia, for example) are selected.
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The number of risk alleles are also selected.
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Using a complicated formula, these two factors are what go
into computing a GRS:
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Understanding what different
genetic risk scores mean
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In order for us to understand what different GRS scores
mean, we can look at two pretend patients.
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Patient 1: AA, GG, TT, CT, AG, TT, GG / Patient 2: GG, GG, TT,
TT, GC, CC, GC
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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).
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http://www.columbiamedicine.org/divisions/gharavi/calc_g
enetic.php
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Applying it to schizophrenia
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Applying it to schizophrenia
(cont.)
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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.
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They found that GRS did not correlate with age, SIRP
performance, parental SES, or IQ.
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There were no significant correlations between GRS and
cumulative and current drug doses, nor negative/positive
symptoms.
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Score didn’t differ between gender, diagnostic group, or
race.
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What does it mean?
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GRS for schizophrenia positively correlated with increased
working memory (WM)-related DLPFC activity.
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However, GRS could not be correlated with symptom
severity, population stratification, or group difference in WM
performance.
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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.
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http://sites.duke.edu/danbelsky/tag/genetic-risk-score/
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http://cran.rproject.org/web/packages/gtx/vignettes/ashg2012.pdf
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http://ghr.nlm.nih.gov/handbook/genomicresearch/snp
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http://web.archive.org/web/20110909085812/http://www.sz
gene.org/TopResults.asp