Evidence map›Paper›PMID 29291710›Full record

ArticleBMC bioinformatics2018

Simulating autosomal genotypes with realistic linkage disequilibrium and a spiked-in genetic effect.

M Shi, D M Umbach, A S Wise, C R Weinberg

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC bioinformatics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. PGsim: A Comprehensive and Highly Customizable Personal Genome Simulator.Frontiers in bioengineering and biotechnology · 2020
    Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

M ShiBiostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA. shi2@niehs.nih.gov.ORCID 0000-0001-8265-5307
D M UmbachBiostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
A S WiseBiostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.
C R WeinbergBiostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, Durham, NC, USA.

Funding

Extending the Phenotype of Nonsyndromic Orofacial CleftsR01DE016148 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MARAZITA, MARY L., WEINBERG, SETH M · 2004 to 2018
$19.7M
PHENOTYPE AND GENETICS IN OROFACIAL CLEFT FAMILIESP50DE016215 · NIDCR · UNIVERSITY OF IOWA · PI LOVETT, MICHAEL · 2004 to 2008
$10.1M
Molecular Genetic Epidemiology of Cleft Lip and PalateR37DE008559 · NIDCR · UNIVERSITY OF IOWA · PI MURRAY, JEFFREY C · 2004 to 2013
$6.8M
International Genetic Epidemiology of Oral CleftsR01DE014581 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI BEATY, TERRI H · 2004 to 2013
$6.6M
Genome Wide Association Coordinating CenterU01HG004446 · NHGRI · UNIVERSITY OF WASHINGTON · PI WEIR, BRUCE S. · 2007 to 2011
$6.6M
Statistical Methods For Genetic EpidemiologyZIAES040007 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WEINBERG, CLARICE · 2009 to 2025
$6.5M
SNP DISCOVERY AND ANALYSIS IN CRANIOFACIAL BIRTH DEFECTSR01DE013939 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI SCOTT, ALAN F · 2000 to 2004
$4.3M
International Consortium to Identify Genes and Interactions Controlling Oral ClefU01DE018993 · NIDCR · JOHNS HOPKINS UNIVERSITY · PI BEATY, TERRI H · 2007 to 2008
$1.6M
GENETIC MAPPING STUDIES OF ORAL-FACIAL CLEFTS IN CHINAR01DE009886 · NIDCR · VIRGINIA COMMONWEALTH UNIVERSITY · PI MARAZITA, MARY L · 1992 to 2002
$1.0M
STATISTICAL METHODS IN REPRODUCTIVE EPIDEMIOLOGYZ01ES040007 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI WEINBERG, CLARICE · 1997 to 2008
$512k
Planning International Orofacial Cleft Genetic StudiesR21DE016930 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MARAZITA, MARY L · 2006 to 2007
$293k
Intramural NIH HHS Z01 ES040007NHGRI NIH HHS U01 HG004446NIDCR NIH HHS P50 DE016215NIDCR NIH HHS R01 DE009886NIDCR NIH HHS R01 DE013939NIDCR NIH HHS R01 DE014581NIDCR NIH HHS R01 DE016148NIDCR NIH HHS R21 DE016930NIDCR NIH HHS R37 DE008559NIDCR NIH HHS U01 DE018993NIEHS NIH HHS Z01 ES040007
6 · The paper itself

Abstract

backgroundTo evaluate statistical methods for genome-wide genetic analyses, one needs to be able to simulate realistic genotypes. We here describe a method, applicable to a broad range of association study designs, that can simulate autosome-wide single-nucleotide polymorphism data with realistic linkage disequilibrium and with spiked in, user-specified, single or multi-SNP causal effects.

resultsOur construction uses existing genome-wide association data from unrelated case-parent triads, augmented by including a hypothetical complement triad for each triad (same parents but with a hypothetical offspring who carries the non-transmitted parental alleles). We assign offspring qualitative or quantitative traits probabilistically through a specified risk model and show that our approach destroys the risk signals from the original data. Our method can simulate genetically homogeneous or stratified populations and can simulate case-parents studies, case-control studies, case-only studies, or studies of quantitative traits. We show that allele frequencies and linkage disequilibrium structure in the original genome-wide association sample are preserved in the simulated data. We have implemented our method in an R package (TriadSim) which is freely available at the comprehensive R archive network.

conclusionWe have proposed a method for simulating genome-wide SNP data with realistic linkage disequilibrium. Our method will be useful for developing statistical methods for studying genetic associations, including higher order effects like epistasis and gene by environment interactions.

Indexed as

Computer SimulationGenotypeLinkage DisequilibriumModels, GeneticPolymorphism, Single NucleotideAlgorithmsAllelesCase-Control StudiesGene FrequencyGenetic Association StudiesGenome-Wide Association StudyHumansPhenotypeCase-parent triadsEpistasisGenome-wide associationGenotype simulationLinkage disequilibrium

Identifiers

PMID29291710
PMCPMC5749028

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.