Evidence map›Paper›PMID 33789345›Full record

ArticleGenetics2021

The genetic architecture of human complex phenotypes is modulated by linkage disequilibrium and heterozygosity.

Dominic Holland, Oleksandr Frei, Rahul Desikan, Chun-Chieh Fan, Alexey A Shadrin, Olav B Smeland, Ole A Andreassen, Anders M Dale

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In one paragraph

Article in Genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 3 pooled it
–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

12 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Review
  6. Whole-genome sequencing study in Koreans identifies novel loci for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Article
  7. Article
  8. Review
  9. Article
  10. Genomics and Functional Genomics of Alzheimer's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Review
  11. Article
  12. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Dominic HollandCenter for Multimodal Imaging and Genetics, University of California at San Diego, La Jolla, CA 92037, USA.
Oleksandr FreiNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo 0424, Norway.
Rahul DesikanDepartment of Radiology, University of California, San Francisco, San Francisco, CA 94158, USA.
Chun-Chieh FanCenter for Multimodal Imaging and Genetics, University of California at San Diego, La Jolla, CA 92037, USA.
Alexey A ShadrinNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo 0424, Norway.
Olav B SmelandNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo 0424, Norway.
Ole A AndreassenNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo 0424, Norway.
Anders M DaleDepartment of Radiology, University of California, San Francisco, San Francisco, CA 94158, USA.

Funding

ABCD-USA Consortium: Data Analysis, Informatics and Resource CenterU24DA041123 · NIDA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANDERS M DALE · 2015 to 2026
$51.5M
NIDA NIH HHS U24 DA041123
6 · The paper itself

Abstract

We propose an extended Gaussian mixture model for the distribution of causal effects of common single nucleotide polymorphisms (SNPs) for human complex phenotypes that depends on linkage disequilibrium (LD) and heterozygosity (H), while also allowing for independent components for small and large effects. Using a precise methodology showing how genome-wide association studies (GWASs) summary statistics (z-scores) arise through LD with underlying causal SNPs, we applied the model to GWAS of multiple human phenotypes. Our findings indicated that causal effects are distributed with dependence on total LD and H, whereby SNPs with lower total LD and H are more likely to be causal with larger effects; this dependence is consistent with models of the influence of negative pressure from natural selection. Compared with the basic Gaussian mixture model it is built on, the extended model-primarily through quantification of selection pressure-reproduces with greater accuracy the empirical distributions of z-scores, thus providing better estimates of genetic quantities, such as polygenicity and heritability, that arise from the distribution of causal effects.

Indexed as

HeterozygoteLinkage DisequilibriumMultifactorial InheritancePolymorphism, Single NucleotideHumansModels, GeneticPhenotypeeffect sizeheritabilitylinkage disequilibriumminor allele frequencynatural selectionpolygenicity

Identifiers

PMID33789345
PMCPMC8045737

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.