Efficient Implementation of Penalized Regression for Genetic Risk Prediction

Genetics
Florian PrivéMichael G B Blum

Abstract

Polygenic Risk Scores (PRS) combine genotype information across many single-nucleotide polymorphisms (SNPs) to give a score reflecting the genetic risk of developing a disease. PRS might have a major impact on public health, possibly allowing for screening campaigns to identify high-genetic risk individuals for a given disease. The "Clumping+Thresholding" (C+T) approach is the most common method to derive PRS. C+T uses only univariate genome-wide association studies (GWAS) summary statistics, which makes it fast and easy to use. However, previous work showed that jointly estimating SNP effects for computing PRS has the potential to significantly improve the predictive performance of PRS as compared to C+T. In this paper, we present an efficient method for the joint estimation of SNP effects using individual-level data, allowing for practical application of penalized logistic regression (PLR) on modern datasets including hundreds of thousands of individuals. Moreover, our implementation of PLR directly includes automatic choices for hyper-parameters. We also provide an implementation of penalized linear regression for quantitative traits. We compare the performance of PLR, C+T and a derivation of random forests using both real a...Continue Reading

References

Jul 1, 1989·Medical Decision Making : an International Journal of the Society for Medical Decision Making·D K McClish
Mar 26, 1971·Science·L B Lusted
Nov 7, 2003·Biometrics·Lori E Dodd, Margaret S Pepe
Aug 21, 2007·Genetics in Medicine : Official Journal of the American College of Medical Genetics·A Cecile J W JanssensMuin J Khoury
Sep 6, 2007·Genome Research·Naomi R WrayPeter M Visscher
Jul 3, 2009·Nature·UNKNOWN International Schizophrenia ConsortiumPamela Sklar
Mar 2, 2010·Nature Genetics·Patrick C A DuboisDavid A van Heel
Jun 22, 2010·Nature Genetics·Jian YangPeter M Visscher
May 12, 2012·BMC Bioinformatics·Gad AbrahamMichael Inouye
Apr 5, 2013·PLoS Genetics·Frank Dudbridge
Jun 5, 2013·American Journal of Human Genetics·Zhi WeiUNKNOWN International IBD Genetics Consortium
Nov 14, 2014·PLoS Genetics·Sebastian OkserTero Aittokallio
Mar 1, 2012·Journal of the Royal Statistical Society. Series B, Statistical Methodology·Robert TibshiraniRyan J Tibshirani
Jan 9, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Nora PashayanPaul D Pharoah
Oct 3, 2015·American Journal of Human Genetics·Bjarni J VilhjálmssonAlkes L Price
May 4, 2016·Nature Reviews. Genetics·Nilanjan ChatterjeeMontserrat García-Closas
Apr 4, 2017·American Journal of Human Genetics·Alicia R MartinEimear E Kenny
Nov 8, 2017·Genetic Epidemiology·Carla Márquez-LunaAlkes L Price
Aug 29, 2018·Genetics·Louis LelloStephen D H Hsu
Oct 12, 2018·Nature·Clare BycroftJonathan Marchini
Dec 18, 2018·American Journal of Human Genetics·Nasim MavaddatDouglas F Easton

❮ Previous
Next ❯

Citations

May 8, 2020·Journal of Medical Genetics·Chantal Babb de VilliersSowmiya Moorthie
May 9, 2021·American Journal of Human Genetics·Clara AlbiñanaBjarni J Vilhjálmsson
Apr 18, 2021·Diabetes Care·Arshiya MariamDaniel M Rotroff
Jan 15, 2022·European Journal of Human Genetics : EJHG·Eileen O DarengPaul D P Pharoah

❮ Previous
Next ❯

Software Mentioned

package
PLR
bigstatsr
PLR3
bigsnpr
Trees
R package bigstatsr
CMSA
gBLUP
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.