The IMAGEN study: a decade of imaging genetics in adolescents
Authors: Mascarell Maričić Lea , Walter Henrik , Rosenthal Annika , Ripke Stephan , Quinlan Erin Burke , Banaschewski Tobias , Barker Gareth J. , Bokde Arun L. W. , Bromberg Uli , Büchel Christian , Desrivières Sylvane , Flor Herta , Frouin Vincent , Garavan Hugh , Itterman Bernd , Martinot Jean-Luc , Martinot Marie-Laure Paillère , Nees Frauke , Orfanos Dimitri Papadopoulos , Paus Tomáš , Poustka Luise , Hohmann Sarah , Smolka Michael N. , Fröhner Juliane H. , Whelan Robert , Kaminski Jakob , Schumann Gunter , Heinz Andreas ,   IMAGEN consortium, Albrecht Lisa , Andrew Chris , Arroyo Mercedes , Artiges Eric , Aydin Semiha , Bach Christine , Banaschewski Tobias , Barbot Alexis , Barker Gareth , Boddaert Nathalie , Bokde Arun , Bricaud Zuleima , Bromberg Uli , Bruehl Ruediger , Büchel Christian , Cachia Arnaud , Cattrell Anna , Conrod Patricia , Constant Patrick , Dalley Jeffrey , Decideur Benjamin , Desrivieres Sylvane , Fadai Tahmine , Flor Herta , Frouin Vincent , Gallinat Jürgen , Garavan Hugh , Briand Fanny Gollier , Gowland Penny , Heinrichs Bert , Heinz Andreas , Heym Nadja , Hübner Thomas , Ireland James , Ittermann Bernd , Jia Tianye , Lathrop Mark , Lanzerath Dirk , Lawrence Claire , Lemaitre Hervé , Lüdemann Katharina , Macare Christine , Mallik Catherine , Mangin Jean-François , Mann Karl , Martinot Jean-Luc , Mennigen Eva , de Carvahlo Fabiana Mesquita , Mignon Xavier , Miranda Ruben , Müller Kathrin , Nees Frauke , Nymberg Charlotte , Paillere Marie-Laure , Paus Tomas , Pausova Zdenka , Poline Jean-Baptiste , Poustka Luise , Rapp Michael , Robert Gabriel , Reuter Jan , Rietschel Marcella , Ripke Stephan , Robbins Trevor , Rodehacke Sarah , Rogers John , Romanowski Alexander , Ruggeri Barbara , Schmäl Christine , Schmidt Dirk , Schneider Sophia , Schumann MarkGunter , Schubert Florian , Schwartz Yannick , Smolka Michael , Sommer Wolfgang , Spanagel Rainer , Speiser Claudia , Spranger Tade , Stedman Alicia , Steiner Sabina , Stephens Dai , Strache Nicole , Ströhle Andreas , Struve Maren , Subramaniam Naresh , Topper Lauren , Walter Henrik , Whelan Robert , Williams Steve , Yacubian Juliana , Zilbovicius Monica , Wong C. Peng , Lubbe Steven , Martinez-Medina Lourdes , Fernandes Alinda , Tahmasebi Amir 
Published: June 2020

Imaging genetics offers the possibility of detecting associations between genotype and brain structure as well as function, with effect sizes potentially exceeding correlations between genotype and behavior. However, study results are often limited due to small sample sizes and methodological differences, thus reducing the reliability of findings. The IMAGEN cohort with 2000 young adolescents assessed from the age of 14 onwards tries to eliminate some of these limitations by offering a longitudinal approach and sufficient sample size for analyzing gene-environment interactions on brain structure and function. Here, we give a systematic review of IMAGEN publications since the start of the consortium. We then focus on the specific phenotype ‘drug use’ to illustrate the potential of the IMAGEN approach. We describe findings with respect to frontocortical, limbic and striatal brain volume, functional activation elicited by reward anticipation, behavioral inhibition, and affective faces, and their respective associations with drug intake. In addition to describing its strengths, we also discuss limitations of the IMAGEN study. Because of the longitudinal design and related attrition, analyses are underpowered for (epi-) genome-wide approaches due to the limited sample size. Estimating the generalizability of results requires replications in independent samples. However, such densely phenotyped longitudinal studies are still rare and alternative internal cross-validation methods (e.g., leave-one out, split-half) are also warranted. In conclusion, the IMAGEN cohort is a unique, very well characterized longitudinal sample, which helped to elucidate neurobiological mechanisms involved in complex behavior and offers the possibility to further disentangle genotype × phenotype interactions.