Missing single nucleotide polymorphisms in Genetic Risk Scores: A simulation study

PloS One
Miguel ChagnonMarie-Pierre Sylvestre

Abstract

Using a genetic risk score (GRS) to predict a phenotype in a target sample can be complicated by missing data on the single nucleotide polymorphisms (SNPs) that comprise the GRS. This is usually addressed by imputation, omission of the SNPs or by replacing the missing SNPs with proxy SNPs. To assess the impact of the omission and proxy approaches on effect size estimation and predictive ability of weighted and unweighted GRS with small numbers of SNPs, we simulated a dichotomous phenotype conditional on real genotype data. We considered scenarios in which the proportion of missing SNPs ranged from 20-70%. We assessed the impact of omitting or replacing missing SNPs on the association between the GRS and phenotype, the corresponding statistical power and the area under the receiver operating curve. Omission resulted in a larger bias towards the null value of the effect size, a smaller predictive ability and greater loss of statistical power than proxy approaches. The predictive ability of a weighted GRS that includes SNPs with large weights depends of the availability of these large-weight SNPs.

References

Jun 27, 1990·JAMA : the Journal of the American Medical Association·J D Watson, R M Cook-Deegan
May 29, 1998·Circulation·P W WilsonW B Kannel
Jun 19, 2007·Nature Genetics·Jonathan MarchiniPeter Donnelly
Nov 1, 2008·Bioinformatics·Andrew D JohnsonPaul I W de Bakker
Apr 9, 2009·Nature Biotechnology·Eran Halperin, Dietrich A Stephan
Jul 3, 2009·Nature·UNKNOWN International Schizophrenia ConsortiumPamela Sklar
Sep 4, 2009·European Journal of Epidemiology·Najaf AminA Cecile J W Janssens
Oct 12, 2010·Nature Genetics·Elizabeth K SpeliotesRuth J F Loos
Jan 15, 2011·Current Protocols in Human Genetics·Stephen TurnerMarylyn D Ritchie
Feb 5, 2011·Human Genetics·Kiranmoy DasRongling Wu
May 1, 2012·Nature Methods·Laura ClarkeUNKNOWN 1000 Genomes Project Consortium
Apr 5, 2013·PLoS Genetics·Frank Dudbridge
Oct 24, 2014·Bioinformatics·Christian FuchsbergerDavid A Hinds
May 24, 2015·American Journal of Hypertension·Caitlin J SmithKelli K Ryckman
Jul 23, 2015·Genetic Epidemiology·Benjamin A GoldsteinThemistoclies L Assimes
Jan 11, 2016·American Journal of Human Genetics·Brian L Browning, Sharon R Browning
Apr 12, 2016·Genetic Epidemiology·Frank Dudbridge
Aug 30, 2016·Nature Genetics·Sayantan DasChristian Fuchsberger
Jul 1, 2017·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Ali ArabkhazaeliAnke H Maitland-van der Zee
Jul 22, 2017·Cancer Prevention Research·Motoki IwasakiUNKNOWN Japan Public Health Center-based Prospective Study (JPHC Study) Group

❮ Previous
Next ❯

Software Mentioned

IMPUTE
minimac
genetics
GenABEL
pROC
SNAP
BEAGLE
LDlink
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.