Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies

James J. Lee, Matt McGue, William G. Iacono, Carson C. Chow
doi: https://doi.org/10.1101/234815
James J. Lee
1Department of Psychology, University of Minnesota Twin Cities, 75 East River Parkway, Minneapolis, MN 55455, USA, (612) 625-4980
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: leex2293@umn.edu carsonc@niddk.nih.gov
Matt McGue
1Department of Psychology, University of Minnesota Twin Cities, 75 East River Parkway, Minneapolis, MN 55455, USA, (612) 625-4980
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William G. Iacono
1Department of Psychology, University of Minnesota Twin Cities, 75 East River Parkway, Minneapolis, MN 55455, USA, (612) 625-4980
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carson C. Chow
2Mathematical Biology Section, Laboratory of Biological Modeling, NIDDK, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA, (301) 402-8250
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: leex2293@umn.edu carsonc@niddk.nih.gov
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

In order to infer that a single-nucleotide polymorphism (SNP) either affects a phenotype or is linkage disequilibrium with a causal site, we must have some assurance that any SNP-phenotype correlation is not the result of confounding with environmental variables that also affect the trait. In this work we study the properties of LD Score regression, a recently developed method for using summary statistics from genome-wide association studies (GWAS) to ensure that confounding does not inflate the number of false positives. We do not treat the effects of genetic variation as a random variable and thus are able to obtain results about the unbiasedness of this method. We demonstrate that LD Score regression can produce estimates of confounding at null SNPs that are unbiased or conservative under fairly general conditions. This robustness holds in the case of the parent genotype affecting the offspring phenotype through some environmental mechanism, despite the resulting correlation over SNPs between LD Scores and the degree of confounding. Additionally, we demonstrate that LD Score regression can produce reasonably robust estimates of the genetic correlation, even when its estimates of the genetic covariance and the two univariate heritabilities are substantially biased.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
Back to top
PreviousNext
Posted May 26, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies
James J. Lee, Matt McGue, William G. Iacono, Carson C. Chow
bioRxiv 234815; doi: https://doi.org/10.1101/234815
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
The accuracy of LD Score regression as an estimator of confounding and genetic correlations in genome-wide association studies
James J. Lee, Matt McGue, William G. Iacono, Carson C. Chow
bioRxiv 234815; doi: https://doi.org/10.1101/234815

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4658)
  • Biochemistry (10313)
  • Bioengineering (7636)
  • Bioinformatics (26241)
  • Biophysics (13481)
  • Cancer Biology (10650)
  • Cell Biology (15363)
  • Clinical Trials (138)
  • Developmental Biology (8467)
  • Ecology (12776)
  • Epidemiology (2067)
  • Evolutionary Biology (16794)
  • Genetics (11373)
  • Genomics (15431)
  • Immunology (10580)
  • Microbiology (25087)
  • Molecular Biology (10172)
  • Neuroscience (54234)
  • Paleontology (398)
  • Pathology (1660)
  • Pharmacology and Toxicology (2884)
  • Physiology (4326)
  • Plant Biology (9213)
  • Scientific Communication and Education (1582)
  • Synthetic Biology (2545)
  • Systems Biology (6761)
  • Zoology (1459)