Evidence map›Paper›PMID 30202041›Full record

ArticleEuropean journal of human genetics : EJHG2019

Exploring predictive biomarkers from clinical genome-wide association studies via multidimensional hierarchical mixture models.

Takahiro Otani, Hisashi Noma, Shonosuke Sugasawa, Aya Kuchiba, Atsushi Goto, Taiki Yamaji, Yuta Kochi, Motoki Iwasaki, Shigeyuki Matsui, Tatsuhiko Tsunoda

Abstract read
In one paragraph

Article in European journal of human genetics : EJHG, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Novel Approaches to Characterize Individual Drug Metabolism and Advance Precision Medicine.Drug metabolism and disposition: the biological fate of chemicals · 2023
    Review
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

10 authors.

Takahiro OtaniDepartment of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. otani@med.nagoya-u.ac.jp.ORCID http://orcid.org/0000-0002-4007-7817
Hisashi NomaDepartment of Data Science, The Institute of Statistical Mathematics, Tachikawa, Tokyo, Japan.
Shonosuke SugasawaCenter for Spatial Information Science, The University of Tokyo, Kashiwa, Chiba, Japan.
Aya KuchibaDivision of Biostatistical Research, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, Japan.
Atsushi GotoDivision of Epidemiology, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, Japan.
Taiki YamajiDivision of Epidemiology, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, Japan.
Yuta KochiLaboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Motoki IwasakiDivision of Epidemiology, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, Japan.
Shigeyuki MatsuiDepartment of Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
Tatsuhiko TsunodaDepartment of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.ORCID http://orcid.org/0000-0002-5439-7918

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although the detection of predictive biomarkers is of particular importance for the development of accurate molecular diagnostics, conventional statistical analyses based on gene-by-treatment interaction tests lack sufficient statistical power for this purpose, especially in large-scale clinical genome-wide studies that require an adjustment for multiplicity of a huge number of tests. Here we demonstrate an alternative efficient multi-subgroup screening method using multidimensional hierarchical mixture models developed to overcome this issue, with application to stroke and breast cancer randomized clinical trials with genomic data. We show that estimated effect size distributions of single nucleotide polymorphisms (SNPs) associated with outcomes, which could provide clues for exploring predictive biomarkers, optimizing individualized treatments, and understanding biological mechanisms of diseases. Furthermore, using this method we detected three new SNPs that are associated with blood homocysteine levels, which are strongly associated with the risk of stroke. We also detected six new SNPs that are associated with progression-free survival in breast cancer patients.

Indexed as

SoftwareBreast NeoplasmsFemaleGenetic TestingGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotideStroke

Identifiers

PMID30202041
PMCPMC6303260

What OpenQuestion holds

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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.