※ 本業績情報は国立研究開発法人科学技術振興機構が運営するサービス「Researchmap」に登録されている研究者データ(プロフィール、業績等)を元に表示しています。

研究業績に対する検索条件
※ スペース区切りで絞り込み検索が可能です。
研究業績タイプによる絞り込み条件です。絞り込みは行っていません。
論文
タイトル
タイトル(英)
Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci.
参照URL
https://researchmap.jp/narcolepsy/published_papers/34753856
著者
著者(英)
Aditya Ambati,Ryan Hillary,Smaranda Leu-Semenescu,Hanna M Ollila,Ling Lin,Emmanuel H During,Neal Farber,Thomas J Rico,Juliette Faraco,Eileen Leary,Andrea N Goldstein-Piekarski,Yu-Shu Huang,Fang Han,Yakov Sivan,Michel Lecendreux,Pauline Dodet,Makoto Honda,Natan Gadoth,Sona Nevsimalova,Fabio Pizza,Takashi Kanbayashi,Rosa Peraita-Adrados,Guy D Leschziner,Rosa Hasan,Francesca Canellas,Kazuhiko Kume,Makrina Daniilidou,Patrice Bourgin,David Rye,José L Vicario,Birgit Hogl,Seung Chul Hong,Guiseppe Plazzi,Geert Mayer,Anne Marie Landtblom,Yves Dauvilliers,Isabelle Arnulf,Emmanuel Jean-Marie Mignot
概要
概要(英)
Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case-control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2 = 0.15; P < 2.0 × 10-22 at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.
出版者・発行元
出版者・発行元(英)
誌名
誌名(英)
Proceedings of the National Academy of Sciences of the United States of America
118
12
開始ページ
終了ページ
出版年月
2021年3月23日
査読の有無
査読有り
招待の有無
掲載種別
研究論文(学術雑誌)
ISSN
DOI URL
https://doi.org/10.1073/pnas.2005753118
共同研究・競争的資金等の研究課題
研究者
本多 真 (ホンダ マコト)