SUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits DOI Creative Commons
Yiliang Zhang, Qiongshi Lu, Yixuan Ye

et al.

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: Sept. 7, 2021

Local genetic correlation quantifies the similarity of complex traits in specific genomic regions. However, accurate estimation local remains challenging, due to linkage disequilibrium regions and sample overlap across studies. We introduce SUPERGNOVA, a statistical framework estimate correlations using summary statistics from genome-wide association demonstrate that SUPERGNOVA outperforms existing methods through simulations analyses 30 traits. In particular, we show positive yet paradoxical between autism spectrum disorder cognitive performance could be explained by two etiologically distinct signatures with bidirectional correlations.

Language: Английский

MVP predicts the pathogenicity of missense variants by deep learning DOI Creative Commons

Hongjian Qi,

Haicang Zhang, Yige Zhao

et al.

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Jan. 21, 2021

Abstract Accurate pathogenicity prediction of missense variants is critically important in genetic studies and clinical diagnosis. Previously published methods have facilitated the interpretation but limited performance. Here, we describe MVP (Missense Variant Pathogenicity prediction), a new method that uses deep residual network to leverage large training data sets many correlated predictors. We train model separately genes are intolerant loss function ones tolerant order take account potentially different effect size mode action. compile cancer mutation hotspots de novo from developmental disorders for benchmarking. Overall, achieves better performance prioritizing pathogenic than previous methods, especially variants. Finally, using MVP, estimate coding contribute 7.8% isolated congenital heart disease, nearly doubling estimates.

Language: Английский

Citations

150
Mutations disrupting neuritogenesis genes confer risk for cerebral palsy DOI
Sheng Chih Jin, Sara A. Lewis,

Somayeh Bakhtiari

et al.

Nature Genetics, Journal Year: 2020, Volume and Issue: 52(10), P. 1046 - 1056

Published: Sept. 28, 2020

Language: Английский

Citations

147
Genetics of Congenital Heart Disease DOI Creative Commons
Kylia Williams, Jason Christopher Carson, Cecilia Lo

et al.

Biomolecules, Journal Year: 2019, Volume and Issue: 9(12), P. 879 - 879

Published: Dec. 16, 2019

Congenital heart disease (CHD) is one of the most common birth defects. Studies in animal models and humans have indicated a genetic etiology for CHD. About 400 genes been implicated CHD, encompassing transcription factors, cell signaling molecules, structural proteins that are important development. Recent studies shown encoding chromatin modifiers, cilia related proteins, cilia-transduced pathways play roles CHD pathogenesis. Elucidating will help improve diagnosis development new therapies to patient outcomes.

Language: Английский

Citations

146
Genomics, convergent neuroscience and progress in understanding autism spectrum disorder DOI
Helen Rankin Willsey, A. Jeremy Willsey, Belinda Wang

et al.

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(6), P. 323 - 341

Published: April 19, 2022

Language: Английский

Citations

140
SUPERGNOVA: local genetic correlation analysis reveals heterogeneous etiologic sharing of complex traits DOI Creative Commons
Yiliang Zhang, Qiongshi Lu, Yixuan Ye

et al.

Genome biology, Journal Year: 2021, Volume and Issue: 22(1)

Published: Sept. 7, 2021

Local genetic correlation quantifies the similarity of complex traits in specific genomic regions. However, accurate estimation local remains challenging, due to linkage disequilibrium regions and sample overlap across studies. We introduce SUPERGNOVA, a statistical framework estimate correlations using summary statistics from genome-wide association demonstrate that SUPERGNOVA outperforms existing methods through simulations analyses 30 traits. In particular, we show positive yet paradoxical between autism spectrum disorder cognitive performance could be explained by two etiologically distinct signatures with bidirectional correlations.

Language: Английский

Citations

134