mTADA is a framework for identifying risk genes from de novo mutations in multiple traits.

Nature Communications
Tan-Hoang NguyenEli Ayumi Stahl

Abstract

Joint analysis of multiple traits can result in the identification of associations not found through the analysis of each trait in isolation. Studies of neuropsychiatric disorders and congenital heart disease (CHD) which use de novo mutations (DNMs) from parent-offspring trios have reported multiple putatively causal genes. However, a joint analysis method designed to integrate DNMs from multiple studies has yet to be implemented. We here introduce multiple-trait TADA (mTADA) which jointly analyzes two traits using DNMs from non-overlapping family samples. We first demonstrate that mTADA is able to leverage genetic overlaps to increase the statistical power of risk-gene identification. We then apply mTADA to large datasets of >13,000 trios for five neuropsychiatric disorders and CHD. We report additional risk genes for schizophrenia, epileptic encephalopathies and CHD. We outline some shared and specific biological information of intellectual disability and CHD by conducting systems biology analyses of genes prioritized by mTADA.

References

Oct 3, 1998·American Journal of Human Genetics·D B AllisonN J Schork
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jul 18, 2006·Journal of Autism and Developmental Disorders·Ovsanna T LeyferJanet E Lainhart
Dec 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Bernard CrespiMichael Elliot
Mar 23, 2011·Current Neurology and Neuroscience Reports·Roberto Tuchman, Michael Cuccaro
Oct 9, 2012·American Journal of Human Genetics·Menachem FromerShaun M Purcell
Jun 12, 2013·Nature Reviews. Genetics·Nadia SolovieffJordan W Smoller
Aug 13, 2013·Nature Genetics·UNKNOWN Cross-Disorder Group of the Psychiatric Genomics ConsortiumUNKNOWN International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)
Aug 13, 2013·Nature·Andrew S AllenMelodie R Winawer
Jan 28, 2014·Nature·Menachem FromerMichael C O'Donovan
Apr 4, 2014·Nature·Jeremy A MillerEd S Lein
Apr 26, 2014·PloS One·Tessel E GaleslootSita H Vermeulen
May 29, 2014·Nature Neuroscience·Alexander HoischenEvan E Eichler
Oct 28, 2014·International Journal of Molecular Sciences·Bao ZhangSheng-Bin Li
Nov 5, 2014·Nature·Silvia De RubeisJoseph D Buxbaum
Jan 8, 2016·Genome Medicine·Janson WhiteV Reid Sutton
Mar 5, 2016·American Journal of Human Genetics·Holly A F StessmanTjitske Kleefstra
May 18, 2016·Nature Genetics·Joseph K PickrellDavid A Hinds
Aug 2, 2016·Nature Neuroscience·Stefan H LelieveldChristian Gilissen
Nov 1, 2016·Bioinformatics·Gleb KichaevBogdan Pasaniuc
Oct 28, 2016·Nature Neuroscience·Giulio GenoveseSteven A McCarroll
Dec 3, 2016·Genetic Epidemiology·Sharon M LutzChristoph Lange
Dec 8, 2016·Nucleic Acids Research·Damian SzklarczykChristian von Mering
Jan 20, 2017·Lancet Neurology·UNKNOWN Epi4K consortium, UNKNOWN Epilepsy Phenome/Genome Project
Jan 31, 2017·Nature·UNKNOWN Deciphering Developmental Disorders Study
May 5, 2017·Neuron·A Jeremy WillseyGary A Heiman
Nov 4, 2017·American Journal of Human Genetics·Fadi F HamdanJacques L Michaud
Jan 3, 2018·Nature Genetics·Patrick TurleyDaniel J Benjamin
Mar 9, 2018·Nature Communications·Robert M MaierMatthew R Robinson
May 23, 2018·Nature Genetics·Nathan G SkeneJens Hjerling-Leffler
Jun 27, 2018·Nature Genetics·Henrike O HeyneJohannes R Lemke

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Methods Mentioned

BETA
scRNAseq
RNAseq
exome sequencing

Software Mentioned

HDIV
SIFT
MutationTaster
EWCE
Seq
rstan
mclust
PROVEAN
BrainSpan
Plink

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