Open Access
A population-specific HTR2B stop codon predisposes to severe impulsivity
Laura Bevilacqua,Stéphane Doly,Jaakko Kaprio,Jaakko Kaprio,Qiaoping Yuan,Roope Tikkanen,Tiina Paunio,Zhifeng Zhou,Juho Wedenoja,Juho Wedenoja,Luc Maroteaux,Silvina L. Diaz,Arnauld Belmer,Colin A. Hodgkinson,Liliana Dell'Osso,Jaana Suvisaari,Emil F. Coccaro,Richard J. Rose,Leena Peltonen,Matti Virkkunen,David Goldman +20 more
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TLDR
In this paper, a stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses.Abstract:
Impulsivity, describing action without foresight, is an important feature of several psychiatric diseases, suicidality and violent behaviour. The complex origins of impulsivity hinder identification of the genes influencing it and the diseases with which it is associated. Here we perform exon-focused sequencing of impulsive individuals in a founder population, targeting fourteen genes belonging to the serotonin and dopamine domain. A stop codon in HTR2B was identified that is common (minor allele frequency > 1%) but exclusive to Finnish people. Expression of the gene in the human brain was assessed, as well as the molecular functionality of the stop codon, which was associated with psychiatric diseases marked by impulsivity in both population and family-based analyses. Knockout of Htr2b increased impulsive behaviours in mice, indicative of predictive validity. Our study shows the potential for identifying and tracing effects of rare alleles in complex behavioural phenotypes using founder populations, and indicates a role for HTR2B in impulsivity.read more
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Journal ArticleDOI
Frequent pathway mutations of splicing machinery in myelodysplasia
Kenichi Yoshida,Masashi Sanada,Yuichi Shiraishi,Daniel Nowak,Yasunobu Nagata,Ryo Yamamoto,Yusuke Sato,Aiko Sato-Otsubo,Ayana Kon,Masao Nagasaki,George Chalkidis,Yutaka Suzuki,Masashi Shiosaka,Ryoichiro Kawahata,Tomoyuki Yamaguchi,Makoto Otsu,Naoshi Obara,Mamiko Sakata-Yanagimoto,Ken Ishiyama,Hiraku Mori,Florian Nolte,Wolf-Karsten Hofmann,Shuichi Miyawaki,Sumio Sugano,Claudia Haferlach,H. Phillip Koeffler,H. Phillip Koeffler,Lee Yung Shih,Torsten Haferlach,Shigeru Chiba,Hiromitsu Nakauchi,Satoru Miyano,Seishi Ogawa +32 more
TL;DR: The results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia.
Journal ArticleDOI
A high-coverage genome sequence from an archaic Denisovan individual
Matthias Meyer,Martin Kircher,Marie Theres Gansauge,Heng Li,Fernando Racimo,Swapan Mallick,Swapan Mallick,Joshua G. Schraiber,Flora Jay,Kay Prüfer,Cesare de Filippo,Peter H. Sudmant,Can Alkan,Can Alkan,Qiaomei Fu,Qiaomei Fu,Ron Do,Nadin Rohland,Nadin Rohland,Arti Tandon,Arti Tandon,Michael Siebauer,Richard E. Green,Katarzyna Bryc,Adrian W. Briggs,Udo Stenzel,Jesse Dabney,Jay Shendure,Jacob O. Kitzman,Michael F. Hammer,Michael V. Shunkov,A.P. Derevianko,Nick Patterson,Aida M. Andrés,Evan E. Eichler,Evan E. Eichler,Montgomery Slatkin,David Reich,David Reich,Janet Kelso,Svante Pääbo +40 more
TL;DR: The genomic sequence provides evidence for very low rates of heterozygosity in the Denisova, probably not because of recent inbreeding, but instead because of a small population size, and illuminates the relationships between humans and archaics, including Neandertals, and establishes a catalog of genetic changes within the human lineage.
Journal ArticleDOI
Impulsivity, compulsivity, and top-down cognitive control.
TL;DR: The results indicate that the vulnerability to stimulant addiction may depend on an impulsivity endophenotype, and characterize in neurobehavioral and neurochemical terms a rodent model of impulsivity based on premature responding in an attentional task.
Journal ArticleDOI
Fractionating impulsivity: neuropsychiatric implications
TL;DR: What is currently known about the neural and psychological mechanisms of impulsivity are reviewed, and the relevance and application of these new insights to various neuropsychiatric disorders are discussed.
Journal ArticleDOI
Dopamine, serotonin and impulsivity
TL;DR: The significance of this heterogeneity for clinical disordersExpressing impulsive behaviour and the pivotal contribution made by the brain dopamine and serotonin systems in the aetiology and treatment of behavioural syndromes expressing impulsive symptoms are discussed.
References
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Journal ArticleDOI
Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene
Avshalom Caspi,Karen Sugden,Terrie E. Moffitt,Alan Taylor,Ian W. Craig,Hona Lee Harrington,Joseph L. McClay,Jonathan Mill,Judy Martin,Antony W. Braithwaite,Richie Poulton +10 more
TL;DR: Evidence of a gene-by-environment interaction is provided, in which an individual's response to environmental insults is moderated by his or her genetic makeup.
Journal ArticleDOI
Role of Genotype in the Cycle of Violence in Maltreated Children
Avshalom Caspi,Avshalom Caspi,Joseph L. McClay,Terrie E. Moffitt,Terrie E. Moffitt,Jonathan Mill,Judy Martin,Ian W. Craig,Alan Taylor,Richie Poulton +9 more
TL;DR: In this paper, a large sample of male children from birth to adulthood was studied to determine why some children who are maltreated grow up to develop antisocial behavior, whereas others do not.
Journal ArticleDOI
Frequent pathway mutations of splicing machinery in myelodysplasia
Kenichi Yoshida,Masashi Sanada,Yuichi Shiraishi,Daniel Nowak,Yasunobu Nagata,Ryo Yamamoto,Yusuke Sato,Aiko Sato-Otsubo,Ayana Kon,Masao Nagasaki,George Chalkidis,Yutaka Suzuki,Masashi Shiosaka,Ryoichiro Kawahata,Tomoyuki Yamaguchi,Makoto Otsu,Naoshi Obara,Mamiko Sakata-Yanagimoto,Ken Ishiyama,Hiraku Mori,Florian Nolte,Wolf-Karsten Hofmann,Shuichi Miyawaki,Sumio Sugano,Claudia Haferlach,H. Phillip Koeffler,H. Phillip Koeffler,Lee Yung Shih,Torsten Haferlach,Shigeru Chiba,Hiromitsu Nakauchi,Satoru Miyano,Seishi Ogawa +32 more
TL;DR: The results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia.
Journal ArticleDOI
A high-coverage genome sequence from an archaic Denisovan individual
Matthias Meyer,Martin Kircher,Marie Theres Gansauge,Heng Li,Fernando Racimo,Swapan Mallick,Swapan Mallick,Joshua G. Schraiber,Flora Jay,Kay Prüfer,Cesare de Filippo,Peter H. Sudmant,Can Alkan,Can Alkan,Qiaomei Fu,Qiaomei Fu,Ron Do,Nadin Rohland,Nadin Rohland,Arti Tandon,Arti Tandon,Michael Siebauer,Richard E. Green,Katarzyna Bryc,Adrian W. Briggs,Udo Stenzel,Jesse Dabney,Jay Shendure,Jacob O. Kitzman,Michael F. Hammer,Michael V. Shunkov,A.P. Derevianko,Nick Patterson,Aida M. Andrés,Evan E. Eichler,Evan E. Eichler,Montgomery Slatkin,David Reich,David Reich,Janet Kelso,Svante Pääbo +40 more
TL;DR: The genomic sequence provides evidence for very low rates of heterozygosity in the Denisova, probably not because of recent inbreeding, but instead because of a small population size, and illuminates the relationships between humans and archaics, including Neandertals, and establishes a catalog of genetic changes within the human lineage.
Journal ArticleDOI
Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A
TL;DR: Analytical results indicate that isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.