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Open AccessJournal ArticleDOI

Clinical use of current polygenic risk scores may exacerbate health disparities.

TLDR
To realize the full and equitable potential of polygenic risk scores, greater diversity must be prioritized in genetic studies, and summary statistics must be publically disseminated to ensure that health disparities are not increased for those individuals already most underserved.
Abstract
Polygenic risk scores (PRS) are poised to improve biomedical outcomes via precision medicine. However, the major ethical and scientific challenge surrounding clinical implementation of PRS is that those available today are several times more accurate in individuals of European ancestry than other ancestries. This disparity is an inescapable consequence of Eurocentric biases in genome-wide association studies, thus highlighting that-unlike clinical biomarkers and prescription drugs, which may individually work better in some populations but do not ubiquitously perform far better in European populations-clinical uses of PRS today would systematically afford greater improvement for European-descent populations. Early diversifying efforts show promise in leveling this vast imbalance, even when non-European sample sizes are considerably smaller than the largest studies to date. To realize the full and equitable potential of PRS, greater diversity must be prioritized in genetic studies, and summary statistics must be publically disseminated to ensure that health disparities are not increased for those individuals already most underserved.

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Citations
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The mutational constraint spectrum quantified from variation in 141,456 humans

TL;DR: A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.
Journal ArticleDOI

Analysis of polygenic risk score usage and performance in diverse human populations

TL;DR: 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.
Journal ArticleDOI

Polygenic risk scores: from research tools to clinical instruments

TL;DR: How polygenic risk score may be informative at different points in the disease trajectory is considered giving examples of progress in the field and discussing obstacles that need to be addressed before clinical implementation.
Journal ArticleDOI

The genetic architecture of Parkinson's disease

TL;DR: Multiple efforts have been made to investigate the genetic architecture of Parkinson's disease, and emerging technologies, such as machine learning, single-cell RNA sequencing, and high-throughput screens, will improve the understanding of genetic risk.
References
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Journal ArticleDOI

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TL;DR: In this review the usual methods applied in systematic reviews and meta-analyses are outlined, and the most common procedures for combining studies with binary outcomes are described, illustrating how they can be done using Stata commands.
Journal ArticleDOI

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Adam Auton, +517 more
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TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
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Biological insights from 108 schizophrenia-associated genetic loci

Stephan Ripke, +354 more
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TL;DR: Associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses.
Journal ArticleDOI

Genome-wide association study identifies novel breast cancer susceptibility loci

Douglas F. Easton, +109 more
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Journal ArticleDOI

A reference panel of 64,976 haplotypes for genotype imputation

Shane A. McCarthy, +117 more
- 22 Aug 2016 - 
TL;DR: A reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies.
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A global reference for human genetic variation.

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Trending Questions (1)
How do the health needs of the Silent Generation differ from the health needs of other generations?

The provided paper does not discuss the health needs of the Silent Generation or compare them to the health needs of other generations.