Genetic risk for autism and other neuropsychiatric conditions, sex differences in neurobiology and risk for disease
- 5262 Genetics and Biotechnology Center
- Research Interests
- Genetic risk for autism and other neuropsychiatric conditions, sex differences in neurobiology and risk for disease
- Research Fields
- Human Genetics, Functional Genomics, Neuropsychiatric Genetics, Biology of Sex Differences
- B.S., Duke University; Ph.D., UCLA; Postdoctoral Research, UCSF
- Lab Website
Genetic variants contribute to risk for neurodevelopmental disorders, many of which show sex differences in their prevalence or presentation. This suggests a potential role for sex-differential biology in modulating the impact of genetic and other risk factors, such that one sex is sensitized and/or the other is protected from risk. One particularly striking example is autism spectrum disorder (ASD): Males are diagnosed with ASD at least three times more frequently than females, and this skew is one of the most consistent, yet mechanistically unexplained, features of ASD. The aim of my research is to understand the key neurobiological mechanisms involved in the etiology of ASD and other neurodevelopmental disorders, including genetic and developmental processes, with a focus on the role of sex-differential biology in modulating risk. Genome-scale analyses are especially powerful for unbiased discovery, and so my lab uses genome-wide genetics, functional genomics, and bioinformatics approaches (e.g. RNA-seq, single cell analyses, eQTLs) in human tissue and model systems to identify and characterize the mechanisms involved in sex-differential and disorder-associated neurobiology. The long-term goal of this research program is to uncover fundamental etiological pathways in both sexes that will facilitate treatment development and benefit affected individuals and their families.
Werling DM*, Pochareddy S*, Choi J*, An J-A*, Sheppard B, Peng M, Li Z, Dastmalchi C, Santpere G, Sousa AMM, Tebbenkamp ATN, Kaur N, Gulden FO, Breen MS, Liang L, Gilson MC, Zhao X, Dong S, Klei L, Cicek AE, Buxbaum JD, Adle-Biassette H, Thomas J-L, Aldinger KA, O’Day DR, Glass IA, Zaitlen NA, Talkowski ME, Roeder K, State MW, Devlin B, Sanders SJ, and Sestan N. Whole-genome and RNA sequencing reveal variation and transcriptomic coordination in the developing human prefrontal cortex. (Under review). See preprint at https://www.biorxiv.org/content/10.1101/585430v1. doi: https://doi.org/10.1101/585430. *These authors contributed equally to this work.
Werling DM*, Brand H*, An J-A*, Stone MR*, Zhu L*, Glessner JT, Collins RL, Dong S, Layer RM, Markenscoff-Papadimitriou E-C, Farrell A, Schwartz GB, Wang HZ, Currall BB, Zhao X, Dea J, Duhn C, Erdman C, Gilson M, Yadav R, Handsaker RE, Kashin S, Klei L, Mandell JD, Nowakowski TJ, Liu Y, Pochareddy S, Smith L, Walker MF, Waterman MJ, He X, Kriegstein AR, Rubenstein JL, Sestan N, McCarroll SA, Neale BM, Coon H, Willsey AJ, Buxbaum JD, Daly MJ, State MW, Quinlan A, Marth GT, Roeder K, Devlin B, Talkowski ME, Sanders SJ. An analytical framework for whole-genome sequence data and its implications for autism spectrum disorder. Nature Genetics, 50, 727-736, 2018. doi: 10.1038/s41588-018-0107-y. PMID: 29700473. *These authors contributed equally to this work.
Werling DM. The role of sex-differential biology in risk for autism spectrum disorder. Biology of Sex Differences, 7(1), 58, 2016. doi: 10.1186/s13293-016-0112-8. PMID: 27891212.
Werling DM, Parikshak NN, & Geschwind DH. Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders. Nature Communications, 7, 10717, 2016. doi: 10.1038/ncomms10717. PMID: 26892004.
Werling DM & Geschwind DH. Recurrence rates provide evidence for sex-differential, familial genetic liability for autism spectrum disorders in multiplex families and twins. Molecular Autism, 6(27), 1-14, 2015. PMID: 25973164.
Lowe JK, Werling DM, Constantino JN, Cantor RM, & Geschwind DH. Social responsiveness, an autism endophenotype: Genomewide significant linkage to two regions on chromosome 8. American Journal of Psychiatry, 172(3), 266-275, 2015. doi: 10.1176/appi.ajp.2014.14050576. PMID: 25727539.
Werling DM, Lowe JK, Luo R, Cantor RM, & Geschwind DH. Replication of linkage for autism spectrum disorder at chromosome 20p13 and identification of suggestive sex-differential risk loci. Molecular Autism, 5(1), 13, 2014. PMID: 24533643.