Analysis of shared heritability in common disorders of the brain
Anttila V., Bulik-Sullivan B., Finucane H. K., Walters R. K., Bras J., Duncan L., Escott-Price V., Falcone G. J., Gormley P., Malik R., Patsopoulos N. A., Ripke S., Wei Z., Yu D., Lee P. H., Turley P., Grenier-Boley B., Chouraki V., Kamatani Y., Berr C., Letenneur L., Hannequin D., Amouyel P., Boland A., Deleuze J. -., Duron E., Vardarajan B. N., Reitz C., Goate A. M., Huentelman M. J., Ilyas K. M., Larson E. B., Rogaeva E., George-Hyslop P. S., Hakonarson H., Kukull W. A., Farrer L. A., Barnes L. L., Beach T. G., Yesim D. F., Head E., Hulette C. M., Jicha G. A., Kauwe J. S. K., Kaye J. A., Leverenz J. B., Levey A. I., Lieberman A. P., Pankratz V. S., Poon W. W., Quinn J. F., Saykin A. J., Schneider L. S., Smith A. G., Sonnen J. A., Stern R. A., Van D. V. M., Van E. L. J., Harold D., Russo G., Rubinsztein D. C., Bayer A., Tsolaki M., Proitsi P., Fox N. C., Hampel H., Owen M. J., Mead S., Passmore P., Morgan K., Nöthen M. M., Rossor M., Lupton M. K., Hoffmann P., Kornhuber J., Lawlor B., McQuillin A., Al-Chalabi A., Bis J. C., Rui
Science
Vol.360, Issue6395, Num.8757
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1126/science.aap8757
Аннотация:
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American
Ключевые слова:
brain; disability; epidemiology; genetic analysis; genome; heritability; nervous system disorder; risk factor; symptom; Alzheimer disease; anorexia nervosa; Article; attention deficit disorder; bipolar disorder; brain ischemia; cognition; comorbidity; controlled study; educational status; genetic association; genetic risk; genetic variability; genome-wide association study; Gilles de la Tourette syndrome; heritability; human; major depression; mental disease; migraine; neurologic disease; neurosis; onset age; phenotype; priority journal; schizophrenia; brain disease; classification; genetic variation; genetics; mental disease; quantitative trait; risk factor; Brain Diseases; Genetic Variation; Genome-Wide Association Study; Humans; Mental Disorders; Phenotype; Quantitative Trait, Heritable; Risk Factors
Язык текста: Английский
ISSN: 1095-9203
Anttila V.
Bulik-Sullivan B.
Finucane H. K.
Walters R. K.
Bras J.
Duncan L.
Escott-Price V.
Falcone G. J.
Gormley P.
Malik R.
Patsopoulos N. A.
Ripke S.
Wei Z.
Yu D.
Lee P. H.
Turley P.
Grenier-Boley B.
Chouraki V.
Kamatani Y.
Berr C.
Letenneur L.
Hannequin D.
Amouyel P.
Boland A.
Deleuze J. -. J.-F.
Duron E.
Vardarajan B. N.
Reitz C.
Goate A. M.
Huentelman M. J.
Ilyas K. M. Kamboh M.
Larson E. B.
Rogaeva E.
George-Hyslop P. S.
Hakonarson H.
Kukull W. A.
Farrer L. A.
Barnes L. L.
Beach T. G.
Yesim D. F. Demirci F.
Head E.
Hulette C. M.
Jicha G. A.
Kauwe J. S. K.
Kaye J. A.
Leverenz J. B.
Levey A. I.
Lieberman A. P.
Pankratz V. S.
Poon W. W.
Quinn J. F.
Saykin A. J.
Schneider L. S.
Smith A. G.
Sonnen J. A.
Stern R. A.
Van D. V. M. Deerlin V.M.
Van E. L. J. Eldik L.J.
Harold D.
Russo G.
Rubinsztein D. C.
Bayer A.
Tsolaki M.
Proitsi P.
Fox N. C.
Hampel H.
Owen M. J.
Mead S.
Passmore P.
Morgan K.
Nöthen M. M.
Rossor M.
Lupton M. K.
Hoffmann P.
Kornhuber J.
Lawlor B.
McQuillin A.
Al-Chalabi A.
Bis J. C.
Rui
Анттила В.
Булик-Сулливан Б.
Финуcане Х. К.
Wалтерс Р. К.
Брас Й.
Дунcан Л.
Есcотт-Приcе В.
Фалcоне Г. Й.
Гормлеy П.
Малик Р.
Пацопоулос Н. А.
Рипке С.
Wеи З.
Д.
Лее П. Х.
Тюрлеy П.
Грениер-Болеy Б.
Чоураки В.
Каматани Y.
Берр C.
Летеннеур Л.
Ханнеqуин Д.
Амоуьел П.
Боланд А.
Делеузе Й. -. Й.-Ф.
Дурон Е.
Вардарайан Б. Н.
Реитз C.
Гоате А. М.
Хуентелман М. Й.
Иляс К. М. Камбох М.
Ларсон Е. Б.
Рогаева Е.
Георге-Хyслоп П. С.
Хаконарсон Х.
Кукулл W. А.
Фаррер Л. А.
Барнес Л. Л.
Беач Т. Г.
Ьесим Д. Ф. Демирcи Ф.
Хеад Е.
Хулетте C. М.
Йича Г. А.
Кауwе Й. С. К.
Кайе Й. А.
Леверенз Й. Б.
Левеy А. И.
Лиеберман А. П.
Панкратз В. С.
Поон W. W.
Qуинн Й. Ф.
Сайкин А. Й.
Счнеидер Л. С.
Смитх А. Г.
Соннен Й. А.
Стерн Р. А.
Ван Д. В. М. Деерлин В.М.
Ван Е. Л. Й. Елдик Л.Й.
Харолд Д.
Руссо Г.
Рубинсзтеин Д. C.
Байер А.
Цолаки М.
Проици П.
Фох Н. C.
Хампел Х.
Оwен М. Й.
Меад С.
Пассморе П.
Морган К.
Нöтхен М. М.
Россор М.
Луптон М. К.
Хоффманн П.
Корнхубер Й.
Лаwлор Б.
МcQуиллин А.
Ал-Чалаби А.
Бис Й. C.
Руи
Analysis of shared heritability in common disorders of the brain
Текст визуальный непосредственный
Science
American Association for the Advancement of Science
Vol.360, Issue6395 Num.8757
2018
Статья
brain disability epidemiology genetic analysis genome heritability nervous system disorder risk factor symptom Alzheimer disease anorexia nervosa Article attention deficit disorder bipolar disorder brain ischemia cognition comorbidity controlled study educational status genetic association genetic risk genetic variability genome-wide association study Gilles de la Tourette syndrome heritability human major depression mental disease migraine neurologic disease neurosis onset age phenotype priority journal schizophrenia brain disease classification genetic variation genetics mental disease quantitative trait risk factor Brain Diseases Genetic Variation Genome-Wide Association Study Humans Mental Disorders Phenotype Quantitative Trait, Heritable Risk Factors
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology. © 2018 American