CoChat
Sign Up
Cited by 28Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsGenetic and phenotypic traits in livestock

Don’t throw the baby out with the bathwater: Enabling a bottom-up approach in genome-wide association studies: Figure 1.

Open access
McGuire, Sean E., McGuire, Amy L.·2008·Genome Research
DOI 10.1101/gr.083584.108PMC PMC3960009
Open this paper in CoChat — free accountOpen PDF

Abstract

The current model for conducting genome-wide association studies (GWAS) is primarily phenotype-driven.In this "top-down" approach, the model is the case-control study, where participants are enrolled based on the presence or absence of a clinical phenotype, for example, cardiovascular disease or breast cancer (Pennisi 2007; Wellcome Trust Case Control Consortium 2007).The International HapMap Project has identified a large number of single nucleotide polymorphisms (SNPs) in the human population that enable investigators to genotype subjects for these various polymorphisms and determine associations with a phenotype of interest (Fig. 1A) (International HapMap Consortium et al. 2007).Commercially available SNP arrays allow researchers to easily genotype from 100,000 to 1,000,000 SNPs per individual, providing "whole-genome" coverage (Affymetrix GeneChip System, http://www.affymetrix.com/products/system.affx; Illumina, Inc., http://www.illumina.com/pages.ilmn?ID=39).Typically, only a handful of these SNPs are associated with the particular phenotype under study and are present in only a small fraction of the study population because the minor alleles (variants) tend to be present at low frequencies.The vast majority of SNPs are not associated with the phenotype under study and are ignored because they are not relevant to the phenotype under investigation in the GWAS.For example, the Wellcome Trust Case Control Consortium genotyped 500,000 SNPs in 14,000 cases representing seven common diseases and an additional 3000 controls.From this extensive genotyping (17,000 ‫ן‬ 500,000), they identified 24 independent associations (Wellcome Trust Case Control Consortium 2007).The vast majority of the genotyping was not relevant to the seven phenotypes under investigation.The failure to use this "excess" genotypic information, by allowing future investigators to recontact participants and collect hypothesisdriven phenotypic information not collected in the original study, represents a tremendous missed opportunity.This type of "targeted phenotyping" would maximize the utility of data generated in GWAS and stored in existing databases, such as dbSNP (http://www.ncbi.nlm.nih.gov/projects/SNP/) and dbGaP (http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap).Recently, scientists have begun to examine the functional consequences of human SNPs in the laboratory, based on data available from the HapMap Project and other SNP discovery studies, without any a priori knowledge of a human phenotype associated with a particular SNP.Having identified an interesting phenotype in vitro, the next step is to determine the conse-4

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1101/gr.083584.108

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Signs or traces of selection in the genome could be detected by using a bottom-up or a from genotype to phenotype approach.

    “These signs or traces of selection in the genome could be detected by using a “bottom-up” or a “from genotype to phenotype” approach (McGuire and McGuire, 2008).”

    From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as McGuire and McGuire, 2008

    The paper’s Abstract describes a bottom-up approach that starts with genetic variation and uses targeted phenotyping to investigate its consequences; Figure 1 contrasts this with a phenotype-first approach. Neither passage says this approach detects signs or traces of selection in the genome. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
McGuire, S. E., & McGuire, A. L.
Affiliations
Baylor College of Medicine (US)
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2008-10-30
Volume
18
Issue
11
Pages
1683-1685
ISSN
1088-9051 (ISSN-L)
DOI
10.1101/gr.083584.108
PMC
PMC3960009
OpenAlex
W2015551662
Cited by
28
References
8
Citations by year
2023: 2 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 4 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 5
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Greenwall Foundation
  • Wellcome Trust
  • National Institutes of Health
  • National Human Genome Research Institute (R01HG004333, HG004333)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
Keywords
genome-wide association study, bottom-up approach, single nucleotide polymorphisms, case-control study, dbGaP, dbSNP, HapMap, minor allele frequency
MeSH terms
Genotype, Humans, Phenotype, Genome, Human, Case-Control Studies, Polymorphism, Single Nucleotide, Databases, Genetic, Genome-Wide Association Study

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review