A number of SFARI Investigators, collaborators and Simons Foundation scientists will present their latest research findings related to the genomic and transcriptomic architecture of autism spectrum disorder and other neurodevelopmental conditions at the 2019 annual meeting of the American Society of Human Genetics (ASHG), which will be held October 15–19 in Houston, TX.

A selection of these presentations is highlighted below.

T. Singh, B.M. Neale, M.J. Daly, on behalf of the SCHEMA consortium
Exome sequencing of 25,000 schizophrenia cases and 100,000 controls implicates 10 risk genes and provides insight into shared and distinct genetic risk and biology with other neurodevelopmental disorders

O. Troyanskaya
Decoding the role of regulatory variation in human disease with deep learning methods

N. Ahituv
Massively parallel dissection of human accelerated regions 

S. Gerges, T. Singh, M. Goldman, S. Berretta, S. McCarroll, M. Daly
Human single-cell transcriptomes identify cell-types and states relevant to brain disorders

O. Kanca, J.C. Andrews, P.T. Lee, C. Patel, S. Braddock, A.M. Slavotinek, J.S. Cohen, C.S. Gubbels, K.A. Aldinger, J. Williams, M. Indaram, A. Fatemi, T.W. Yu, P.B. Agrawal, G. Vezina, B. Gangaram, J. Wynn, R. Hernan, G. Mychaliska, W.K. Chung, T.C. Markello, W.B. Dobyns, D.R. Adams, W.A. Gahl,  M.F. Wangler,  S. Yamamoto, H.J. Bellen,  M.C.V. Malicdan, Undiagnosed Disease Network
De novo variants in WDR37 are associated with epilepsy, colobomas, dysmorphism, developmental delay, intellectual disability and cerebellar hypoplasia

M.T. Oetjens, M.A. Kelly, A.C. Strum, Regeneron Genetics Center, C.L. Martin, D.H. Ledbetter
Quantifying the polygenic contribution to variable expressivity in eleven rare genetic disorders

L. Pennacchio
Linking enhancer variation to human disease in vivo

N. Sinnott-Armstrong, Y. Tanigawa, S. Naqvi, N.J. Mars, D. Amar, H.M. Ollila, M. Aguirre, G.R. Venkataraman, M. Wainberg, J.P. Pirruccello, J. Qian, A. Shcherbina, F. Rodriguez, T.L. Assimes, V. Agarwala, R. Tibshirani, T. Hastie, S. Ripatti, M.J. Daly, J.K. Pritchard, M.A. Rivas, FinnGen
Genetics of 38 blood and urine biomarkers in the UK Biobank

J. Stein
Unearthing the evolutionary history of common genetic variants influencing human cortical surface area

X. Zhang, Y. Veturi, A. Verma, T.G. Drivas, W.K. Chung, D. Crosslin, J.C. Denny, D. Fasel, H. Hakonarson, S. Hebbring, G.P. Jarvik, I. Kullo, E.B. Larson, S.A. Pendergrass, L. Rasmussen-Torvik, D. Schaid, P. Sleiman, J.W. Smoller, I.B. Stanaway, W. Wei, C. Weng, M.D. Ritchie
Genetic studies in the eMERGE network and UK Biobank offer new insights into pleiotropy across cardiovascular diseases and central nervous system disorders

W. Zhou, B.M. Neale, M.J. Daly, on behalf of Global Biobank Meta-analysis Initiative
Global Biobank Meta-analysis Initiative: Powering genetic discovery across human diseases

H. Zoghbi
ASHG Victor A. McKusick Leadership Award Presentation and Lecture:
The wonders of genetics: When rare diseases shed light on the common

M. Artomov, A.A. Loboda, M.N. Artyomov, M.J. Daly
Public platform with 42,291 exome control samples enables association studies without genotype sharing

M. Gymrek, S. Feupe Fotsing, C. Wang, S. Saini, R. Yanicky, S. Shleizer-Burko, A. Goren
Multi-tissue analysis reveals short tandem repeats as ubiquitous regulators of gene expression and complex traits

H.O.H. Heyne, S.M.L. Lemmelae, J.K. Karjalainen, A.S.H. Havulinna, A.P. Palotie, M.J.D. Daly
Known disease variants in a population-wide analysis of 135,638 Finns

Y. Li, Z. Li, Y. Kang, E. Allen, H. Wu, Z. Wen, P. Jin
Identification of human-specific mRNA targets of fragile X mental retardation protein

F. Meili, K. Post, M. Belmadani, P. Ganguly, R. Dingwall, T. McDiarmid, C. Harrington, M. Edwards, B. Young, A. Niciforovic, B. Callahan, S. Rogic, W. Meyers, A. Cau, T. O’Connor, C. Rankin, S.X. Bamji, D.W. Allen, C. Loewen, P. Pavlidis, K. Haas
A multi-model approach for deep functional variomic profiling of ASD-associated PTEN missense mutations identifies multiple molecular mechanisms underlying protein dysfunction

T.L. Mighell, C.A. Thornton, B.L. O’Connell, R.M. Mulqueen, C.V. Miller, A.C. Adey, D. Doherty, B.J. O’Roak
CRISPR-capture: A novel, low-cost and scalable method for targeted sequencing

K. Mohajeri, E. D’haene, R. Yadav, H. Gu, B. Menten, A. Presser Aiden, C. Lowther, S. Erdin, M. Moyses Oliveria, P. Boone, E. Lieberman-Aiden, J. Gusella, S. Vergult, M. Talkowski
Mechanistic dissection of chromatin topology disruption as an indirect, strong effect driver of neurodevelopmental disorders

A. O’Donnell-Luria, M.H. Wojcik, K.R. Chao, J.K. Goodrich, L.S. Pais, E. England, E.G. Seaby, A.B. Byrne, B.B. Cummings, R.L. Collins, M. Lek, L. Gallacher, T.Y. Tan, K.M. Bujakowska, E.A. Pierce, P.B. Agrawal, C.A. Walsh, J.M. Verboon, V.G. Sankaran, C. Barnett, H. Scott, W.K. Chung, E.A. Estrella, C.C. Bruels, P.B. Kang, S. Pajusalu, K. Ounap, A.K. Lovgren, H.L. Rehm, D.G. MacArthur
Identifying diagnoses beyond the exome: Lessons from challenging cases with compelling clinical phenotypes

F.K. Satterstrom, J. Fu, H. Brand, J.A. Kosmicki, H. Wang, X. Zhao, R.L. Collins, M.S. Breen, S. De Rubeis, C.E. Carey, C. Stevens, C. Cusick, E.B. Robinson, A.D. Børglum, D.J. Cutler, J.D. Buxbaum, K. Roeder, B. Devlin, S.J. Sanders, M.J. Daly, M.E. Talkowski, Autism Sequencing Consortium
Insights into the genetic architecture of autism from exome and genome sequencing of over 60,000 individuals

S. Thacker, T. Mighell, I.N. Smith, M. Seyfi, B.J. O’Roak, C. Eng
Integrating molecular and clinical phenotypes towards clinical insight on genotype-phenotype relationships for missense germline PTEN variation

M. Zaghlula, J.-Y. Kim, L. Nitschke, H.H. Jeong, C.E. Alcott, J.-P. Revelli, Z. Liu, S.J. Elledge, H.Y. Zoghbi
Identification of post-translational regulators of MeCP2 levels as potential therapeutic targets for MECP2 duplication syndrome

C. Wu, S. Shleizer-Burko, A. Goren, M. Gymrek
Interrogating regulatory consequences of genetic variation in DNA associated proteins

T. Brünger, S. Iqbal, E. Perez-Palma, M.J. Daly, A.J. Campbell, P. May, D. Lal
Identification of functionally essential sites using 3D single protein and multiprotein complexes across 73 neurodevelopmental disorder-associated genes

C.A. Walsh
One brain, many genomes: Somatic mutation and genomic diversity in human brain

R.L. Collins, H. Brand, K.J. Karczewski, X. Zhao, J. Alföldi, A.V. Khera, L.C. Francioli, L.D. Gauthier, H. Wang, N.A. Watts, M. Solomonson, A. O’Donnell-Luria, A. Baumann, R. Munshi, C. Lowther, M. Walker, C. Whelan, E. Valkanas, J. Fu, A. Philippakis, E. Lander, S. Gabriel, B.M. Neale, S. Kathiresan, M.J. Daly, E. Banks, D.G. MacArthur, M.E. Talkowski, The Genome Aggregation (gnomAD) Consortium
gnomAD-SV: An open resource of structural variation for medical and population genetics

A. Farrell, W. Richards, A. Docherty, H. Coon, G. Marth
The unbiased length spectrum of human de novo mutations in 4,330 children

D.F. Hannum, H. Yao, S.F. Hill, R.D. Albanus, W. Lou, J.M. Skidmore, G.J. Sanchez, A. Saiakhova, S.L. Bielas, P.C. Scacheri, M. Ljungman, S.C.J. Parker, D.M. Martin
The ATP-dependent chromatin remodeler CHD7 is critical for neuronal lineage differentiation by changing chromatin accessibility and nascent RNA

A. Kreimer, F. Inoue, T. Ashuach, N. Ahituv, N. Yosef
Massively parallel characterization of regulatory dynamics during neural induction

C.A. Thornton, A. Mishra, A.P. Barnes, B.J. O’Roak, A.C. Adey
Spatially resolved single-cell chromatin accessibility in the adult mouse brain