Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing
Corominas J., Klein M., Zayats T., Rivero O., Ziegler G. C., Pauper M., Neveling K., Poelmans G., Jansch C., Svirin E. P., Geissler J., Weber H., Reif A., Arias V. A., Galesloot T. E., Kiemeney L. A. L. M., Buitelaar J. K., Ramos-Quiroga J. -., Cormand B., Ribasés M., Hveem K., Gabrielsen M. E., Hoffmann P., Cichon S., Haavik J., Johansson S., Jacob C. P., Romanos M., Franke B., Lesh K. Yu.
Molecular Psychiatry
Vol.25, Issue9, P. 2047-2057
Опубликовано: 2020
Тип ресурса: Статья
DOI:10.1038/s41380-018-0210-6
Аннотация:
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a complex genetic background, hampering identification of underlying genetic risk factors. We hypothesized that combining linkage analysis and whole-exome sequencing (WES) in multi-generation pedigrees with multiple affected individuals can point toward novel ADHD genes. Three families with multiple ADHD-affected members (Ntotal = 70) and apparent dominant inheritance pattern were included in this study. Genotyping was performed in 37 family members, and WES was additionally carried out in 10 of those. Linkage analysis was performed using multi-point analysis in Superlink Online SNP 1.1. From prioritized linkage regions with a LOD score ≥ 2, a total of 24 genes harboring rare variants were selected. Those genes were taken forward and were jointly analyzed in gene-set analyses of exome-chip data using the MAGMA software in an independent sample of patients with persistent ADHD and healthy contro
Язык текста: Английский
ISSN: 1476-5578
Corominas J.
Klein M.
Zayats T.
Rivero O.
Ziegler G. C.
Pauper M.
Neveling K.
Poelmans G.
Jansch C.
Svirin E. P. Evgenij Pavlovich 1991-
Geissler J.
Weber H.
Reif A.
Arias V. A. Vasquez A.
Galesloot T. E.
Kiemeney L. A. L. M.
Buitelaar J. K.
Ramos-Quiroga J. -. J.-A.
Cormand B.
Ribasés M.
Hveem K.
Gabrielsen M. E.
Hoffmann P.
Cichon S.
Haavik J.
Johansson S.
Jacob C. P.
Romanos M.
Franke B.
Lesh K. Yu. Klaus-Peter Yulius 1957-
Cороминас Й.
Клеин М.
Зайац Т.
Риверо О.
Зиеглер Г. C.
Паупер М.
Невелинг К.
Поелманс Г.
Йансч C.
Свирин Е. П. Евгений Павлович 1991-
Геисслер Й.
Wебер Х.
Реиф А.
Ариас В. А. Васqуез А.
Галеслоот Т. Е.
Киеменеy Л. А. Л. М.
Буителаар Й. К.
Рамос-Qуирога Й. -. Й.-А.
Cорманд Б.
Рибасéс М.
Хвеем К.
Габриелсен М. Е.
Хоффманн П.
Cичон С.
Хаавик Й.
Йоханссон С.
Йаcоб C. П.
Романос М.
Франке Б.
Леш К. Ю. Клаус-Петер Юлиус 1957-
Identification of ADHD risk genes in extended pedigrees by combining linkage analysis and whole-exome sequencing
Текст визуальный непосредственный
Molecular Psychiatry
Nature Publishing Group
Vol.25, Issue9 P. 2047-2057
2020
Статья
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with a complex genetic background, hampering identification of underlying genetic risk factors. We hypothesized that combining linkage analysis and whole-exome sequencing (WES) in multi-generation pedigrees with multiple affected individuals can point toward novel ADHD genes. Three families with multiple ADHD-affected members (Ntotal = 70) and apparent dominant inheritance pattern were included in this study. Genotyping was performed in 37 family members, and WES was additionally carried out in 10 of those. Linkage analysis was performed using multi-point analysis in Superlink Online SNP 1.1. From prioritized linkage regions with a LOD score ≥ 2, a total of 24 genes harboring rare variants were selected. Those genes were taken forward and were jointly analyzed in gene-set analyses of exome-chip data using the MAGMA software in an independent sample of patients with persistent ADHD and healthy contro