Journal Article

The IMAGEN study: a decade of imaging genetics in adolescents

Barbot Alexis, Lubbe, Steven, Fernandes Alinda, Boddaert Nathalie, Ripke Stephan, Schumann MarkGunter, Andrew, Chris, Müller Kathrin, Bruehl Ruediger, Subramaniam Naresh, Miranda, Ruben, Mallik, Catherine, Rapp, Michael, Ruggeri, Barbara, Arroyo, Mercedes, Papadopoulos, Orfanos Dimitri, Romanowski, Alexander, Kaminski, Jakob, Gowland, Penny, Schubert, Florian, Poustka Luise, Mangin Jean-François, Cachia Arnaud, Robbins, Trevor, Schwartz, Yannick, Cattrell Anna, Walter, Henrik, Itterman Bernd, Aydin Semiha, Lathrop, Mark, Steiner, Sabina, Tahmasebi Amir, Lawrence, Claire, Lemaitre Hervé, Schmäl Christine, Nees Frauke, Albrecht, Lisa, Dalley, Jeffrey, Rogers, John, Paus Tomas, Flor Herta, Rosenthal, Annika, Conrod, Patricia, Gabriel, Robert, Martinez-Medina, Lourdes, Garavan Hugh, Reuter, Jan, Bokde Arun, Stephens, Dai, de Carvahlo Fabiana Mesquita, Rietschel Marcella, Rodehacke, Sarah, Bricaud Zuleima, Constant, Patrick, Heinrichs, Bert, Spanagel Rainer, Fadai Tahmine, Whelan, Robert, Frouin Vincent, Mignon Xavier, Peng, Wong C, Paillère, Martinot Marie-Laure, Schneider, Sophia, Martinot Jean-Luc, Hübner, Thomas

2020

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Adolescents / Functional anatomy / Genomes / Genotype & phenotype / Genotypes / Neostriatum / Neuroimaging / Phenotypes / Reinforcement / Structure-function relationships / Systematic review / Teenagers