ArticlePLoS genetics2018
Heritability informed power optimization (HIPO) leads to enhanced detection of genetic associations across multiple traits.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Mendelianization: Concentrating Polygenic Signal Into a Single Causal Locus.Genetic epidemiology · 2026Article
- Dissecting pleiotropy to gain mechanistic insights into human disease.Nature reviews. Genetics · 2026Review
- Large-scale composite hypothesis testing procedure for omics data analyses.NAR genomics and bioinformatics · 2025Article
- Mendelian randomization analysis using multiple biomarkers of an underlying common exposure.Biostatistics (Oxford, England) · 2024Article
- The goldmine of GWAS summary statistics: a systematic review of methods and tools.BioData mining · 2024Article
- Genome-wide large-scale multi-trait analysis characterizes global patterns of pleiotropy and unique trait-specific variants.Nature communications · 2024Article
- JASPER: Fast, powerful, multitrait association testing in structured samples gives insight on pleiotropy in gene expression.American journal of human genetics · 2024Article
- Trait selection strategy in multi-trait GWAS: Boosting SNP discoverability.HGG advances · 2024Article
- Integrative regulation of hLMR1 by dietary and genetic factors in nonalcoholic fatty liver disease and hyperlipidemia.Human genetics · 2024Article
- JASPER: fast, powerful, multitrait association testing in structured samples gives insight on pleiotropy in gene expression.bioRxiv : the preprint server for biology · 2023Article
- Trait selection strategy in multi-trait GWAS: Boosting SNPs discoverability.bioRxiv : the preprint server for biology · 2023Article
- Accurate detection of shared genetic architecture from GWAS summary statistics in the small-sample context.PLoS genetics · 2023Article
- Polygenic influences on the behavioral effects of alcohol withdrawal in a mixed-ancestry population from the collaborative study on the genetics of alcoholism (COGA).Molecular and cellular neurosciences · 2023Article
- A multivariate genome-wide association study of psycho-cardiometabolic multimorbidity.PLoS genetics · 2023Article
- Leveraging pleiotropy for joint analysis of genome-wide association studies with per trait interpretations.PLoS genetics · 2022Article
- Article
- Shared components of heritability across genetically correlated traits.American journal of human genetics · 2022Article
- Gene-based association tests using GWAS summary statistics and incorporating eQTL.Scientific reports · 2022Article
- Multitrait GWAS to connect disease variants and biological mechanisms.PLoS genetics · 2021Article
- Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.Nature genetics · 2021Article
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2 authors.
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Abstract
Genome-wide association studies have shown that pleiotropy is a common phenomenon that can potentially be exploited for enhanced detection of susceptibility loci. We propose heritability informed power optimization (HIPO) for conducting powerful pleiotropic analysis using summary-level association statistics. We find optimal linear combinations of association coefficients across traits that are expected to maximize non-centrality parameter for the underlying test statistics, taking into account estimates of heritability, sample size variations and overlaps across the traits. Simulation studies show that the proposed method has correct type I error, robust to population stratification and leads to desired genome-wide enrichment of association signals. Application of the proposed method to publicly available data for three groups of genetically related traits, lipids (N = 188,577), psychiatric diseases (Ncase = 33,332, Ncontrol = 27,888) and social science traits (N ranging between 161,460 to 298,420 across individual traits) increased the number of genome-wide significant loci by 12%, 200% and 50%, respectively, compared to those found by analysis of individual traits. Evidence of replication is present for many of these loci in subsequent larger studies for individual traits. HIPO can potentially be extended to high-dimensional phenotypes as a way of dimension reduction to maximize power for subsequent genetic association testing.
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