SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy Article Swipe

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Delnaz Roshandel , Eric J. Sanders , Amy Shakeshaft , Naim Panjwani , Lin Fan , Amber Collingwood , Anna Hall , Katherine Keenan , Celine Deneubourg , Filippo Mirabella , Simon Topp , Jana Zárubová , Rhys H. Thomas , Inga Talvik , Marte Syvertsen , Pasquale Striano , Anna Smith , Kaja Kristine Selmer , Guido Rubboli , Alessandro Orsini , Ching Ching Ng , Rikke S. Møller , Kheng Seang Lim , Khalid Hamandi , David A. Greenberg , Joanna Gesche , Elena Gardella , Choong Yi Fong , Christoph P. Beier , Danielle M. Andrade , Heinz Jungbluth , Mark P. Richardson , Annalisa Pastore , Manolis Fanto , Deb K. Pal , Lisa J. Strug , Zuzana Šobíšková , Cechovaz Pracoviste , Michaela Kajšová , Rikke S. Møller , Elena Gardella , M Miranda , Pasquale Striano , Alessandro Orsini , Paulina Bala , Amy Kitching , Kate Irwin , Lorna Walding , Lynsey Adams , Uma Jegathasan , Rachel Swingler , Rachel Wane , Julia Aram , Nikil Sudarsan , Dee Mullan , Rebecca Ramsay , Vivien Richmond , M. Sargent , Paul Frattaroli , Matthew D. Taylor , Marie Home , Sal Uka , Susan Kilroy , Tonicha Nortcliffe , Kheng Seang Lim , Kelly Holroyd , Alison McQueen , Dympna Mcaleer , Dina Jayachandran , Dawn Egginton , Bridget MacDonald , Michael Chang , David Deekollu , Alok Gaurav , Caroline Hamilton , Jaya Natarajan , Inyan Takon , Janet Cotta , Nick Moran , Jeremy D.P. Bland , Rosemary Belderbos , Heather Collier , Joanne Henry , Matthew J. Milner , Sam White , Michalis Koutroumanidis , William Stern , Jennifer M. Quirk , Javier Peña‐Ceballos , Anastasia Papathanasiou , Ioannis Stavropoulos , Dora A. Lozsádi , Andrew Swain , Charlotte Quamina , Jennifer Crooks , Tahir Majeed , Sonia Raj , Shakeelah Patel , Michael C. Young , Melissa Maguire ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1038/s41525-023-00370-z

Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME ( n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 ( P = 7.5 × 10 −9 ) and 10p11.21 ( P = 3.6 × 10 −8 ). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex ( P = 9.5 × 10 −3 ). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes ( P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes ( P = 0.0005) including NLGN1 and PTPRD . RNAi knockdown of Oatp30B , the Drosophila polypeptide with the highest homology to SLCO5A1 , causes over-reactive startling behaviour ( P = 8.7 × 10 −3 ) and increased seizure-like events ( P = 6.8 × 10 −7 ). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME ( P = 1.60 × 10 −3 ). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.

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Juvenile myoclonic epilepsy Impulsivity Epilepsy Juvenile Myoclonic epilepsy Neuroscience Psychology Biology Psychiatry Genetics

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Type: article
Language: en
Landing Page: https://doi.org/10.1038/s41525-023-00370-z
PDF: https://www.nature.com/articles/s41525-023-00370-z.pdf
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DOI: https://doi.org/10.1038/s41525-023-00370-z

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Title: SLCO5A1 and synaptic assembly genes contribute to impulsivity in juvenile myoclonic epilepsy

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Language: en

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Publication year: 2023

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Publication date: 2023-09-28

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Authors: Delnaz Roshandel, Eric J. Sanders, Amy Shakeshaft, Naim Panjwani, Lin Fan, Amber Collingwood, Anna Hall, Katherine Keenan, Celine Deneubourg, Filippo Mirabella, Simon Topp, Jana Zárubová, Rhys H. Thomas, Inga Talvik, Marte Syvertsen, Pasquale Striano, Anna Smith, Kaja Kristine Selmer, Guido Rubboli, Alessandro Orsini, Ching Ching Ng, Rikke S. Møller, Kheng Seang Lim, Khalid Hamandi, David A. Greenberg, Joanna Gesche, Elena Gardella, Choong Yi Fong, Christoph P. Beier, Danielle M. Andrade, Heinz Jungbluth, Mark P. Richardson, Annalisa Pastore, Manolis Fanto, Deb K. Pal, Lisa J. Strug, Zuzana Šobíšková, Cechovaz Pracoviste, Michaela Kajšová, Rikke S. Møller, Elena Gardella, M Miranda, Pasquale Striano, Alessandro Orsini, Paulina Bala, Amy Kitching, Kate Irwin, Lorna Walding, Lynsey Adams, Uma Jegathasan, Rachel Swingler, Rachel Wane, Julia Aram, Nikil Sudarsan, Dee Mullan, Rebecca Ramsay, Vivien Richmond, M. Sargent, Paul Frattaroli, Matthew D. Taylor, Marie Home, Sal Uka, Susan Kilroy, Tonicha Nortcliffe, Kheng Seang Lim, Kelly Holroyd, Alison McQueen, Dympna Mcaleer, Dina Jayachandran, Dawn Egginton, Bridget MacDonald, Michael Chang, David Deekollu, Alok Gaurav, Caroline Hamilton, Jaya Natarajan, Inyan Takon, Janet Cotta, Nick Moran, Jeremy D.P. Bland, Rosemary Belderbos, Heather Collier, Joanne Henry, Matthew J. Milner, Sam White, Michalis Koutroumanidis, William Stern, Jennifer M. Quirk, Javier Peña‐Ceballos, Anastasia Papathanasiou, Ioannis Stavropoulos, Dora A. Lozsádi, Andrew Swain, Charlotte Quamina, Jennifer Crooks, Tahir Majeed, Sonia Raj, Shakeelah Patel, Michael C. Young, Melissa Maguire

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Concepts: Juvenile myoclonic epilepsy, Impulsivity, Epilepsy, Juvenile, Myoclonic epilepsy, Neuroscience, Psychology, Biology, Psychiatry, Genetics

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sustainable_development_goals[0].id	https://metadata.un.org/sdg/3
sustainable_development_goals[0].score	0.7599999904632568
sustainable_development_goals[0].display_name	Good health and well-being
citation_normalized_percentile.value	0.95123653
citation_normalized_percentile.is_in_top_1_percent	False
citation_normalized_percentile.is_in_top_10_percent	True