Genetic architecture of complex traits and disease risk predictors.

Scientific Reports
Soke Yuen YongStephen D. H. Hsu

Abstract

Genomic prediction of complex human traits (e.g., height, cognitive ability, bone density) and disease risks (e.g., breast cancer, diabetes, heart disease, atrial fibrillation) has advanced considerably in recent years. Using data from the UK Biobank, predictors have been constructed using penalized algorithms that favor sparsity: i.e., which use as few genetic variants as possible. We analyze the specific genetic variants (SNPs) utilized in these predictors, which can vary from dozens to as many as thirty thousand. We find that the fraction of SNPs in or near genic regions varies widely by phenotype. For the majority of disease conditions studied, a large amount of the variance is accounted for by SNPs outside of coding regions. The state of these SNPs cannot be determined from exome-sequencing data. This suggests that exome data alone will miss much of the heritability for these traits-i.e., existing PRS cannot be computed from exome data alone. We also study the fraction of SNPs and of variance that is in common between pairs of predictors. The DNA regions used in disease risk predictors so far constructed seem to be largely disjoint (with a few interesting exceptions), suggesting that individual genetic disease risks are la...Continue Reading

References

Nov 21, 2000·American Journal of Human Genetics·G R AbecasisW O Cookson
Mar 14, 2002·Archives of Pediatrics & Adolescent Medicine·Beth S FinkelsteinLeona Cuttler
Jun 25, 2005·Proceedings of the National Academy of Sciences of the United States of America·David L Donoho, Jared Tanner
Jan 18, 2006·Nature Genetics·Struan F A GrantKari Stefansson
Dec 7, 2006·Journal of the National Cancer Institute·Kenneth Offit
May 29, 2007·Nature·Douglas F EastonBruce A J Ponder
Jun 15, 2007·Genome Research·Mark B GersteinMichael Snyder
Jun 15, 2007·Genome Research·Thomas R Gingeras
Jan 10, 2008·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·J M WitP Cohen
Jun 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Owen M WoodwardMichael Köttgen
Oct 7, 2009·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·David Donoho, Jared Tanner
Apr 30, 2010·Journal of the National Cancer Institute·Eitan AmirD Gareth Evans
Sep 3, 2010·Genetics in Medicine : Official Journal of the American College of Medical Genetics·David L VeenstraWylie Burke
Dec 21, 2010·American Journal of Human Genetics·Jian YangPeter M Visscher
Jul 14, 2011·PLoS Biology·Deanna M ChurchTim Hubbard
Sep 8, 2012·Genome Research·Jennifer HarrowTim J Hubbard
Jul 19, 2013·Science Translational Medicine·Howard J JacobElizabeth A Worthey
Jan 10, 2014·Human Molecular Genetics·Simon N StaceyKari Stefansson
May 6, 2014·JAMA : the Journal of the American Medical Association·Laurie E Cohen
Jul 9, 2014·GigaScience·Shashaank VattikutiCarson C Chow
Jul 27, 2014·Heart·James R Priest, Euan A Ashley
Aug 12, 2014·Trends in Genetics : TIG·Erwin L van DijkClaude Thermes
Jan 1, 2015·Bioinformatics·Jack EuesdenPaul F O'Reilly
Apr 10, 2015·Nature Communications·Simon N StaceyKari Stefansson
Jul 27, 2015·Current Opinion in Genetics & Development·Gad Abraham, Michael Inouye
Sep 18, 2015·GigaScience·Chiu Man Ho, Stephen Dh Hsu
Oct 3, 2015·American Journal of Human Genetics·Bjarni J VilhjálmssonNick Patterson
May 4, 2016·Nature Reviews. Genetics·Nilanjan ChatterjeeMontserrat García-Closas
Nov 1, 2016·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sarah BowdinIan D Krantz
Aug 28, 2016·Breast Cancer Research and Treatment·Yiwey ShiehElad Ziv
Apr 1, 2017·Genetics·Petter Portin, Adam Wilkins
Apr 5, 2017·Journal of the National Cancer Institute·Karoline B KuchenbaeckerAntonis C Antoniou
Nov 3, 2017·Open Biology·Sophie Hackinger, Eleftheria Zeggini
Nov 15, 2017·Genome Medicine·Cathryn M Lewis, Evangelos Vassos
Jan 6, 2018·Genome Medicine·Krishna C VadodariaFred H Gage
May 3, 2018·Trends in Genetics : TIG·Urko M MarigortaArcadi Navarro
May 24, 2018·Nature Reviews. Genetics·Ali TorkamaniEric J Topol
Aug 29, 2018·Genetics·Louis LelloStephen D H Hsu

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
genotyping
exome-sequencing
from

Software Mentioned

gnomAD
GENCODE
Ensembl
LASSO

Related Concepts

Related Feeds

Atrial Filbrillation

Atrial fibrillation refers to the abnormal heart rhythm characterized by rapid and irregular beating of the atria. Here is the latest research.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

© 2021 Meta ULC. All rights reserved