ArticleAmerican journal of human genetics2014
Rare-variant extensions of the transmission disequilibrium test: application to autism exome sequence data.
Article in American journal of human genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- Targeted Sequencing and Meta-Analysis of Preterm Birth.PloS one · 2016Pooled it
- T-rex: standardized analysis of germline variants in whole-exome sequencing trios.Scientific reports · 2026Article
- A generalized test of genotype-phenotype causality in population-sampled nuclear families.PLoS genetics · 2026Article
- The oligogenic inheritance test GCOD detects risk genes and their interactions in congenital heart defects.Genome research · 2026Article
- MIRAGE: A Bayesian statistical method for gene-level rare-variant analysis incorporating functional annotations.American journal of human genetics · 2026Article
- Functional Annotation of De Novo Variants Found Near GWAS Loci Associated With Cleft Lip With or Without Cleft Palate.Birth defects research · 2025Article
- Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Whole genome sequencing identifies associations for nonsyndromic sagittal craniosynostosis with the intergenic region of BMP2 and noncoding RNA gene LINC01428.Scientific reports · 2024Article
- Gene-based association tests in family samples using GWAS summary statistics.Genetic epidemiology · 2024Article
- Article
- Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD.Nature communications · 2023Article
- Rare variant modifier analysis identifies variants in SEC24D associated with orofacial cleft subtypes.Human genetics · 2023Article
- Transmission disequilibrium analysis of whole genome data in childhood-onset systemic lupus erythematosus.Genes and immunity · 2023Article
- Rare genetic variants inmedRxiv : the preprint server for health sciences · 2023Article
- Article
- GIGYF1 disruption associates with autism and impaired IGF-1R signaling.The Journal of clinical investigation · 2022Article
- Targeted Sequencing of Candidate Regions Associated with Sagittal and Metopic Nonsyndromic Craniosynostosis.Genes · 2022Article
- Recent advances and challenges of rare variant association analysis in the biobank sequencing era.Frontiers in genetics · 2022Review
- Recent ultra-rare inherited variants implicate new autism candidate risk genes.Nature genetics · 2021Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Many population-based rare-variant (RV) association tests, which aggregate variants across a region, have been developed to analyze sequence data. A drawback of analyzing population-based data is that it is difficult to adequately control for population substructure and admixture, and spurious associations can occur. For RVs, this problem can be substantial, because the spectrum of rare variation can differ greatly between populations. A solution is to analyze parent-child trio data, by using the transmission disequilibrium test (TDT), which is robust to population substructure and admixture. We extended the TDT to test for RV associations using four commonly used methods. We demonstrate that for all RV-TDT methods, using proper analysis strategies, type I error is well-controlled even when there are high levels of population substructure or admixture. For trio data, unlike for population-based data, RV allele-counting association methods will lead to inflated type I errors. However type I errors can be properly controlled by obtaining p values empirically through haplotype permutation. The power of the RV-TDT methods was evaluated and compared to the analysis of case-control data with a number of genetic and disease models. The RV-TDT was also used to analyze exome data from 199 Simons Simplex Collection autism trios and an association was observed with variants in ABCA7. Given the problem of adequately controlling for population substructure and admixture in RV association studies and the growing number of sequence-based trio studies, the RV-TDT is extremely beneficial to elucidate the involvement of RVs in the etiology of complex traits.
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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.