Virtual talk at Boston Children's Hospital

This is a talk on some of our recent work on discovering genetic variants associated with human cortical structure and how those variants influence gene regulatory potential in the developing brain. The talk was given on April 14, 2020 as a virtual seminar on Zoom due to the COVID crisis.

GWAS of Cortical Structure published in Science

As part of the ENIGMA consortium, we published a large study to demonstrate how genetic variation in humans impacts cortical structure. We identified 199 loci that were significantly associated with cortical structure by a stringent criterion. We also found that those genetic variants that influence adult surface area are enriched in genomic regions active in progenitor cells during neuronal differentiation well before birth. This is evidence in humans supporting the Radial Unit Hypothesis, put forward by Pasko Rakic in the 1980s. In addition, there were genetic correlations detected between cortical surface area and several traits including cognitive abilities and ADHD. This implies that genetic variants that impact cortical structure also impact cortical function. You can find our work published here. This is a huge collaboration and wouldn’t be possible without the joint work of literally hundreds of scientists. We started the ENIGMA consortium about 10 years ago, and this is our latest and greatest work. It’s particularly exciting because the structure of the cortex allows us to have human specific abilities and disruption of cortical structure is thought to cause neuropsychiatric disorders.

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Pre-print posted on genome-wide association study in autism using the SPARK dataset

In joint work with the lab of Hyejung Won by joint postdoc Nana Matoba, we used the SPARK dataset to identify common genetic variants associated with risk for Autism Spectrum Disorder. We were able to replicate previous findings and also identify a new locus. For that new locus, we used a multiplex parallel reporter assay (MPRA) to identify a potential causal variant. We integrated this information with existing eQTL resources to identify genes of action for those variants. You can read more about this work in the pre-print here.

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Biorxiv pre-print posted on genetic effects on chromatin accessibility during human neuronal differentiation

Dan Liang, a graduate student in the lab, posted a pre-print of our work on genetic effects on chromatin accessibility in cultured human neural progenitor cells. In this work, we identified thousands of common genetic variants that influence gene regulatory activity during human neuronal differentiation. We use this data to explain the gene regulatory mechanisms of several GWAS loci for neuropsychiatric disorders and brain relevant traits. The preprint can be found here.

Biorxiv pre-print posted on evolutionary genomics of human brain Structure

Together with Simon Fisher and Amanda Tilot, we just submitted a biorxiv pre-print on how genetic variation through our evolutionary history impacted modern human brain structure. Interesting findings include that variation present within human-specific regulatory elements present in the developing cortex, prior to birth, have a strong impact on adult brain structure. And, alleles with evidence of selective pressure over very recent time scales (in evolutionary history) have impacts on specific brain regions, including those involved in spoken language and visual processing. Read more about this work here: https://www.biorxiv.org/content/10.1101/703793v1.

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SPARK grant acquired to identify common variants associated with autism

Our lab and the lab of Hyejung Won (wonlab.org) acquired a grant from the Simons Foundation to identify common genetic variants associated with risk for autism. Our shared postdoc Nana Matoba is working on this project. Thanks to the Simons Foundation for their support and we hope to add to the list of common genetic variants creating risk for autism.

https://www.sfari.org/2019/03/28/sfari-announces-genomic-analysis-for-autism-risk-variants-in-spark-awardees/

Grad students win awards at the UNC Genetics Retreat in Wilmington

Dan Liang was selected to give a talk on the genetic influences of chromatin accessibility during human neuronal differentiation at the UNC genetics retreat in Wilmington, and won the best student talk of the Bioinformatics and Computational Biology program. Congrats Dan! Mike Lafferty presented a poster on miRNAs involved in human neurogenesis and won a best student poster award for the Bioinformatics and Computational Biology program. Congrats Mike!

Moving to Mary Ellen Jones Building at UNC

We are moving on March 19th, along with the UNC Neuroscience Center, to the newly renovated, window filled, Mary Ellen Jones Building! Looks really beautiful and will be a great place to do some genetics and brain science.

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Teaching middle schoolers about the brain

Today we taught some middle school students about how genetics shapes the brain, and let them explore a human brain in virtual reality.

Andrew S. Rachlin UNC Neuroscience Symposium

The Stein lab co-organized the Andrew S. Rachlin UNC Neuroscience Symposium this year. Thanks to Dan Geschwind and Flora Vaccarino for coming as our keynote speakers, and to all the local speakers for a fascinating seminar! Hope it leads to future collaborations and projects on tackling neuropsychiatric disorder genetics here in the triangle area.

Stein lab at the Walk for Hope

We ran the 5k (Jason) and 10k (Tianyi) at the Walk for Hope to raise money for the Foundation of Hope. This is a great organization supporting research into mental health, including supporting some of our work. https://walkforhope.com/