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BY HILLARY EAMES A GROUNDBRE AKING STUDY RE VE ALS AN ULTR A-R ARE GENOMIC VARIANT OF TEN PRESENTS IN PATIENTS WITH SCHIZOPHRENIA, PROVIDING MORE INFORMATION ON EFFECTIVE TRE ATMENT OPTIONS FOR A COMPLICATED DISORDER. THE ROLE OF genetics in the development of schizophre- nia ha s rema ined compa ratively complex to understa nd. Schizophrenia is predominately a heredita r y disease, with patient s bei ng more t ha n si x ti mes a s li kely to present w it h sch i zoph ren ia i f a close relative ha s t he d isorder. Schizophrenia is not caused by a single genetic mutation, but a complex combination of genetic changes with compounding effects. Even as recently as Februar y 2018, the U.S. Nationa l Libra r y of Medicine noted that the way genetic cha nges relate to sch i zoph ren ia a re "not wel l u nderstood," a nd f ur ther knowledge wou ld require robust a nd continuous resea rch. W hi le severa l studies have been per formed to understand how a patient 's genes can lead to the development a nd/or heritabi lit y of the disorder, gaps w ithin resea rch have rema ined. However, g reat strides have been made recently to close t hose gaps . A 2020 s t udy per for med at t he Un iversit y o f No r t h C a r o l i n a a t C h a p e l H i l l a n d p u b l i s h e d i n Nature Communications illustrates a n integra l connection bet ween genomic str uctura l va ria nts a nd schizophrenia . Before this study, research about schizophrenia's heritability prima ri ly rev iewed common genetic va riations in single nucleotide polymorphisms, occurring within a pa r t of DNA that provides instructions on protein synthesis. W hile these studies highlighted por tions of the genome, it was not until Jin Szatkiewicz, PhD, associate professor, Depa r tment of Genetics a nd adjunct a ssista nt professor, Depa r tment of Psychiatr y at the Universit y of Nor th Ca rolina at Chapel Hill a nd her associates used whole-genome sequencing to exa mine the entire genome. The complete picture of the genome led to rema rkable new discoveries: specif ica l ly, va ria nts within topolog ica lly associating doma ins (TA Ds) are more likely to be present in patients with schizophrenia. "Our results suggest that ultra-ra re structura l va ria nts that affect the boundaries of [this] specific genome structure increase the risk of schizophrenia ," Szatkiewicz says in a press release. "A lterations in these bounda ries may lead to dysreg ulation of gene expression." METHODS AND FINDINGS: HOW TAD VARIANTS AFFECT THE BRAIN WITH SCHIZOPHRENIA In this study, the U NC School of Medicine resea rchers found that extremely rare structura l variants within TA D boundaries are significantly more common in patients with schizophrenia tha n in patients without. Structura l va ri- a nts a re la rge mutations with duplicated or missing gene Discovered in Patients With Genomic Structural Variants 1 4