polygenic risk score analysis

The utility of Polygenic Risk Scores (PRS) is gaining researchers' attention for identifying individual genetic risk and disease risk prediction in Alzheimer's Disease (AD) at both the early and pre-symptomatic stages of the disease.

Clipboard, Search History, and several other advanced features are temporarily unavailable. 2020 Jun 25;21(Suppl 2):132. doi: 10.1186/s12881-020-01068-0. A historical tendency to use European ancestry samples hinders medical genetics research, including the use of polygenic scores, which are individual-level metrics of genetic risk.

Each row in the forest plot (left) represents one pair of polygenic analyses (i.e., in a non-European ancestry sample and a matched European ancestry sample from the same study. Mind the gap: why many geneticists and psychological scientists have discrepant views about gene-environment interaction (G×E) research. Phenotypes, citation information, and available effect sizes are given for each comparison. For polygenic score construction,…, Scatterplots of height polygenic scores ( x -axis) and phenotypic height ( y…, NLM 2020 Oct 1;16(10):e1008207.

2016;538:161–164.

Epub 2017 Jun 21. Passchier RV, Stein DJ, Uhlmann A, van der Merwe C, Dalvie S. Front Genet. We analyze the first decade of polygenic scoring studies (2008-2017, inclusive), and find that 67% of studies included exclusively European ancestry participants and another 19% included only East Asian ancestry participants.

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doi: 10.1016/j.ebiom.2015.10.002. Unequal representation of genetic variation across ancestry groups creates healthcare inequality in the application of precision medicine.  |  Genome-Wide Association Studies of Cancer in Diverse Populations.

Polygenic score distributions for the five major 1000Genomes populations are plotted, showing how investigator-driven choices impact score distributions.

-, Duncan LE, Pollastri AR, Smoller JW.

K01 MH113848/MH/NIMH NIH HHS/United States, UL1 TR001085/TR/NCATS NIH HHS/United States, Bustamante CD, Burchard EG, De la Vega FM.

Implicit bias of encoded variables: frameworks for addressing structured bias in EHR-GWAS data.

genoSCORE™ combines Cytox's proprietary technologies variaTECT™, a proprietary single nucleotide polymorphism (SNP) profiling array built on the Axiom platform from Thermo Fisher Scientific, with the SNPfitR™ analytical and interpretive software incorporating algorithms developed in partnership with Cardiff University, to give a PRS that identifies any individual's genetic risk of developing AD from blood or saliva-extracted DNA.

-, Dalvie S, et al.

doi: 10.1038/538161a. -. African ancestry samples: t = -5.97, df = 24, p = 3.7 × 10-6), and we demonstrate the effects of methodological choices in polygenic score distributions for worldwide populations. For polygenic score construction, clumping is often used, and investigator-driven choices can produce large differences in score distributions for global populations. doi: 10.1371/journal.pcbi.1008207. Hum Mol Genet.

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These findings highlight the need for improved treatment of linkage disequilibrium and variant frequencies when applying polygenic scoring to cohorts of non-European ancestry, and bolster the rationale for large-scale GWAS in diverse human populations.

Get the latest public health information from CDC: https://www.coronavirus.gov. EBioMedicine. This site needs JavaScript to work properly. 2016;17:157. doi: 10.1186/s13059-016-1016-y.

Psychol. BMC Med Genet. 2018 Apr;27(4):405-417. doi: 10.1158/1055-9965.EPI-17-0169.

Please enable it to take advantage of the complete set of features! A genotype imputation method for de-identified haplotype reference information by using recurrent neural network.

Ancestry representation in the first decade of polygenic scoring studies (2008–2017; N =…, Forest plot of performance shows variation in polygenic score performance by ancestry (26…, Polygenic score distributions vary by ancestry and methodical choices.

An integrated personal and population-based Egyptian genome reference. HDL-C high density lipoprotein cholesterol, VLDL very low-density lipoprotein, GERA Genetic Epidemiology Research on Aging, OR odds ratio, UKB UK Biobank, IgAN immunoglobulin A nephropathy, AUC area under the curve, BP blood pressure, BMI body mass index, Polygenic score distributions vary by ancestry and methodical choices.

Genet Epidemiol. doi: 10.1093/hmg/ddaa192. eCollection 2020 Oct. García-González J, Ramírez J, Howard DM, Brennan CH, Munroe PB, Keers R. Transl Psychiatry. The application of polygenic risk scores (PRS) has become routine across genetic research.

2014 Apr;38(3):265-73. doi: 10.1002/gepi.21788. HHS 2015;2:1259–1261.  | 

The effects of polygenic risk for psychiatric disorders and smoking behaviour on psychotic experiences in UK Biobank. Accounting for linkage disequilibrium in association analysis of diverse populations. Only 3.8% of studies were among cohorts of African, Hispanic, or Indigenous peoples. Dikilitas O, Schaid DJ, Kosel ML, Carroll RJ, Chute CG, Denny JA, Fedotov A, Feng Q, Hakonarson H, Jarvik GP, Lee MTM, Pacheco JA, Rowley R, Sleiman PM, Stein CM, Sturm AC, Wei WQ, Wiesner GL, Williams MS, Zhang Y, Manolio TA, Kullo IJ. Drug Alcohol Depend. See this image and copyright information in PMC.

We find that predictive performance of European ancestry-derived polygenic scores is lower in non-European ancestry samples (e.g. 2020 Sep 28;10(1):330. doi: 10.1038/s41398-020-01009-8. doi: 10.1037/a0036320. This is a presentation by Dr. Richard Pither, CEO of Cytox Ltd.

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