ASD and ADHD have a similar burden of rare protein-truncating variants

By F. Satterstrom, R. Walters, T. Singh, Emilie M. Wigdor, F. Lescai, D. Demontis, J. Kosmicki, J. Grove, C. Stevens, J. Bybjerg-Grauholm and 12 more. 2018

29 citations recorded by the source corpus.

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are substantially heritable, but individuals with psychiatric diagnoses often do not have blood drawn as part of routine medical procedure, making it difficult to collect large cohorts for genetic study. To overcome this challenge, we drew upon two Danish national resources: the Danish Neonatal Screening Biobank (DNSB) and the Danish national psychiatric registry. We have previously validated the use of archived bloodspots from the DNSB for genotyping and sequencing, and we recently performed common variant analysis on dried bloodspot material in both ASD and ADHD. Here, we present exome sequences from over 13,000 DNSB samples, finding that ASD and ADHD show a strikingly similar burden of rare protein-truncating variants, both significantly higher than controls. Additionally, the distributions of genes hit by these variants are not distinguishable between the two disorders, suggesting that many risk genes may be shared between them. These results motivate a combined analysis across ASD and ADHD, which--in conjunction with incorporation of the gnomAD reference database as additional population controls--leads to the identification of genes conferring general risk for childhood psychiatric disorders, including the novel gene MAP1A.

Subfields: Cellular and Molecular Neuroscience, Genetics, Psychiatry and Mental health

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. Daniel H. Geschwind

In Genetics

1. Benjamin M. Neale
2. Mark J. Daly
3. L. Weiss
4. J. Kosmicki
5. C. Betancur
6. Silvia De Rubeis
7. Kaitlin E. Samocha
8. Konrad J. Karczewski

In Psychiatry and Mental health

1. Carsten B. Pedersen
2. P. Mortensen
3. Dara S. Manoach
4. Daniel H. Geschwind
5. Nancy J. Minshew

Citations in the corpus

• Transcript expression-aware annotation improves rare variant discovery and interpretation (2019, methodology): “We also utilized a previously published dataset of variants in 8,437 cases with ASD and/or attention-deficit/hyperactivity disorder and 5,214 controls from the Danish Neonatal Screening Biobank (48).”
• Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism (2019, methodology): “Of these, 6,197 samples were newly sequenced by our consortium (1,908 cases with parents, 274 additional cases, 25 controls) and 11,265 samples were newly incorporated (416 cases with parents, plus 4,811 additional cases and 5,214 controlsfrom theDanishiPSYCH study;Satterstrom et al.,2018).”