Brain imaging genetics in ADHD and beyond - Mapping pathways from gene to disorder at different levels of complexity.
Attention-deficit/hyperactivity disorder (ADHD) is a common and often persistent neurodevelopmental disorder. Beyond gene-finding, neurobiological parameters, such as brain structure, connectivity, and function, have been used to link genetic variation to ADHD symptomatology. We performed a systematic review of brain imaging genetics studies involving 62 ADHD candidate genes in childhood and adult ADHD cohorts. Fifty-one eligible research articles described studies of 13 ADHD candidate genes. Almost exclusively, single genetic variants were studied, mostly focussing on dopamine-related genes. While promising results have been reported, imaging genetics studies are thus far hampered by methodological differences in study design and analysis methodology, as well as limited sample sizes. Beyond reviewing imaging genetics studies, we also discuss the need for complementary approaches at multiple levels of biological complexity and emphasize the importance of combining and integrating findings across levels for a better understanding of biological pathways from gene to disease. These may include multi-modal imaging genetics studies, bioinformatic analyses, and functional analyses of cell and animal models.
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Marieke
M
Klein
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Marten
M
Onnink
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Marjolein
M
van Donkelaar
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Thomas
T
Wolfers
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Benjamin
B
Harich
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Yan
Y
Shi
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Department of Psychiatry, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Janneke
J
Dammers
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Department of Psychiatry, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Department of Cognitive Neuroscience, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Alejandro
A
Arias-Vásquez
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
Martine
M
Hoogman
Department of Human Genetics, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Department of Psychiatry, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands. Electronic address: barbara.franke@radboudumc.nl.
Barbara
B
Franke
D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology*; D059906:Neuroimaging
ADHD; Animal models; Brain imaging genetics; Candidate genes; Endophenotype