ArticleBMC medical genomics2015
Refining multivariate disease phenotypes for high chip heritability.
Article in BMC medical genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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.
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.
Who cites it
2 citing papers in PubMed.
- Performing post-genome-wide association study analysis: overview, challenges and recommendations.F1000Research · 2021Article
- Lack of Association between Opioid-Receptor Genotypes and Smoking Cessation Outcomes in a Randomized, Controlled Naltrexone Trial.Alcohol and alcoholism (Oxford, Oxfordshire) · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
backgroundStatistical genetics shows that the success of both genetic association studies and genomic prediction methods is positively associated with the heritability of the trait used in the analysis. Identifying highly heritable components of a complex disease can thus enhance genetic studies of the disease. Existing heritable component analysis methods use data from related individuals to compute linearly-combined traits to maximize heritability. Recent advances in acquiring genome-wide markers have enhanced heritability estimation using genotypic data from apparently unrelated individuals, which is referred to as the chip heritability. Novel statistical models are thus needed to identify disease components (subtypes) with high chip heritability.
methodsWe propose an optimization approach to identify highly heritable components of a complex disease as a function of multiple clinical variables. The heritability of the components is estimated directly from unrelated individuals using their genome-wide single nucleotide polymorphisms. The proposed approach can also model the fixed effects due to covariates, such as age and race, so that the derived traits have high chip heritability after correcting for fixed effects. A new sequential quadratic programming algorithm is developed to efficiently solve the proposed optimization problem.
resultsThe proposed algorithm was validated both in simulations and the analysis of a real-world dataset that was aggregated from genetic studies of cocaine, opoid, and alcohol dependence. Simulation studies demonstrated that the proposed approach could identify the hypothesized component from multiple synthesized features. A case study on cocaine dependence (CD) identified a quantitative trait that achieved chip heritability of 0.86 estimated using a cross-validation process. This quantitative trait corresponded to the likelihood of an individual's membership in a CD subtype. Clinical analysis showed that the subtype enclosed individuals who reported heavy use of cocaine but few withdrawal symptoms.
conclusionsExtensive experiments on both synthetic and real-world data demonstrate the effectiveness of the proposed approach as a means to find meaningful disease components with high chip heritability.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.