Browsing by Author "Hirschhorn, Joel N."

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    Genome-wide association study identifies 48 common genetic variants associated with handedness
    (Springer Nature, 2021) Cuellar-Partida, Gabriel; Tung, Joyce Y.; Eriksson, Nicholas; Albrecht, Eva; Aliev, Fazil; Andreassen, Ole A.; Barroso, Inês; Beckmann, Jacques S.; Boks, Marco P.; Boomsma, Dorret I.; Boyd, Heather A.; Breteler, Monique M. B.; Campbell, Harry; Chasman, Daniel I.; Cherkas, Lynn F.; Davies, Gail; de Geus, Eco J. C.; Deary, Ian J.; Deloukas, Panos; Dick, Danielle M.; Duffy, David L.; Eriksson, Johan G.; Esko, Tõnu; Feenstra, Bjarke; Geller, Frank; Gieger, Christian; Giegling, Ina; Gordon, Scott D.; Han, Jiali; Hansen, Thomas F.; Hartmann, Annette M.; Hayward, Caroline; Heikkilä, Kauko; Hicks, Andrew A.; Hirschhorn, Joel N.; Hottenga, Jouke-Jan; Huffman, Jennifer E.; Hwang, Liang-Dar; Ikram, M. Arfan; Kaprio, Jaakko; Kemp, John P.; Khaw, Kay-Tee; Klopp, Norman; Konte, Bettina; Kutalik, Zoltan; Lahti, Jari; Li, Xin; Loos, Ruth J. F.; Luciano, Michelle; Magnusson, Sigurdur H.; Mangino, Massimo; Marques-Vidal, Pedro; Martin, Nicholas G.; McArdle, Wendy L.; McCarthy, Mark I.; Medina-Gomez, Carolina; Melbye, Mads; Melville, Scott A.; Metspalu, Andres; Milani, Lili; Mooser, Vincent; Nelis, Mari; Nyholt, Dale R.; O'Connell, Kevin S.; Ophoff, Roel A.; Palmer, Cameron; Palotie, Aarno; Palviainen, Teemu; Pare, Guillaume; Paternoster, Lavinia; Peltonen, Leena; Penninx, Brenda W. J. H.; Polasek, Ozren; Pramstaller, Peter P.; Prokopenko, Inga; Raikkonen, Katri; Ripatti, Samuli; Rivadeneira, Fernando; Rudan, Igor; Rujescu, Dan; Smit, Johannes H.; Smith, George Davey; Smoller, Jordan W.; Soranzo, Nicole; Spector, Tim D.; St. Pourcain, Beate; Starr, John M.; Stefánsson, Hreinn; Steinberg, Stacy; Teder-Laving, Maris; Thorleifsson, Gudmar; Stefánsson, Kári; Timpson, Nicholas J.; Uitterlinden, André G.; van Duijn, Cornelia M.; van Rooij, Frank J. A.; Vink, Jaqueline M.; Vollenweider, Peter; Vuoksimaa, Eero; Waeber, Gérard; Wareham, Nicholas J.; Warrington, Nicole; Waterworth, Dawn; Werge, Thomas; Wichmann, H-Erich; Widen, Elisabeth; Willemsen, Gonneke; Wright, Alan F.; Wright, Margaret J.; Xu, Mousheng; Zhao, Jing Hua; Kraft, Peter; Hinds, David A.; Lindgren, Cecilia M.; Mägi, Reedik; Neale, Benjamin M.; Evans, David M.; Medland, Sarah E.; Epidemiology, School of Public Health
    Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
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    Whole exome sequencing to identify genetic causes of short stature
    (S. Karger AG, 2014) Guo, Michael H.; Shen, Yiping; Walvoord, Emily C.; Miller, Timothy C.; Moon, Jennifer E.; Hirschhorn, Joel N.; Dauber, Andrew; Department of Pediatrics, IU School of Medicine
    BACKGROUND/AIMS: Short stature is a common reason for presentation to pediatric endocrinology clinics. However, for most patients, no cause for the short stature can be identified. As genetics plays a strong role in height, we sought to identify known and novel genetic causes of short stature. METHODS: We recruited 14 children with severe short stature of unknown etiology. We conducted whole exome sequencing of the patients and their family members. We used an analysis pipeline to identify rare non-synonymous genetic variants that cause the short stature. RESULTS: We identified a genetic cause of short stature in 5 of the 14 patients. This included cases of floating-harbor syndrome, Kenny-Caffey syndrome, the progeroid form of Ehlers-Danlos syndrome, as well as 2 cases of the 3-M syndrome. For the remaining patients, we have generated lists of candidate variants. CONCLUSIONS: Whole exome sequencing can help identify genetic causes of short stature in the context of defined genetic syndromes, but may be less effective in identifying novel genetic causes of short stature in individual families. Utilized in the clinic, whole exome sequencing can provide clinically relevant diagnoses for these patients. Rare syndromic causes of short stature may be underrecognized and underdiagnosed in pediatric endocrinology clinics.