The IMAGEN study: a decade of imaging genetics in adolescents

IMAGEN Consortium

doi:10.1038/s41380-020-0822-5

The IMAGEN study: a decade of imaging genetics in adolescents

IMAGEN Consortium

Research output: Contribution to journal › Review article › peer-review

57 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	2648-2671
Number of pages	24
Journal	Molecular Psychiatry
Volume	25
Issue number	11
DOIs	https://doi.org/10.1038/s41380-020-0822-5
Publication status	Published - 1 Nov 2020

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title = "The IMAGEN study: a decade of imaging genetics in adolescents",

abstract = "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 {\textquoteleft}drug use{\textquoteright} 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.",

author = "{IMAGEN Consortium} and {Mascarell Mari{\v c}i{\'c}}, Lea and Henrik Walter and Annika Rosenthal and Stephan Ripke and Quinlan, {Erin Burke} and Tobias Banaschewski and Barker, {Gareth J.} and Bokde, {Arun L.W.} and Uli Bromberg and Christian B{\"u}chel and Sylvane Desrivi{\`e}res and Herta Flor and Vincent Frouin and Hugh Garavan and Bernd Itterman and Martinot, {Jean Luc} and Martinot, {Marie Laure Paill{\`e}re} and Frauke Nees and Orfanos, {Dimitri Papadopoulos} and Tom{\'a}{\v s} Paus and Luise Poustka and Sarah Hohmann and Smolka, {Michael N.} and Fr{\"o}hner, {Juliane H.} and Robert Whelan and Jakob Kaminski and Gunter Schumann and Andreas Heinz and Lisa Albrecht and Chris Andrew and Mercedes Arroyo and Eric Artiges and Semiha Aydin and Christine Bach and Tobias Banaschewski and Alexis Barbot and Gareth Barker and Nathalie Boddaert and Arun Bokde and Zuleima Bricaud and Anna Cattrell and Patricia Conrod and Tianye Jia and Christine Macare and Catherine Mallik and Charlotte Nymberg and Jan Reuter and Barbara Ruggeri and Maren Struve and Lauren Topper",

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doi = "10.1038/s41380-020-0822-5",

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AU - Martinot, Jean Luc

AU - Martinot, Marie Laure Paillère

AU - Nees, Frauke

AU - Orfanos, Dimitri Papadopoulos

AU - Paus, Tomáš

AU - Poustka, Luise

AU - Hohmann, Sarah

AU - Smolka, Michael N.

AU - Fröhner, Juliane H.

AU - Whelan, Robert

AU - Kaminski, Jakob

AU - Schumann, Gunter

AU - Heinz, Andreas

AU - Albrecht, Lisa

AU - Andrew, Chris

AU - Arroyo, Mercedes

AU - Artiges, Eric

AU - Aydin, Semiha

AU - Bach, Christine

AU - Banaschewski, Tobias

AU - Barbot, Alexis

AU - Barker, Gareth

AU - Boddaert, Nathalie

AU - Bokde, Arun

AU - Bricaud, Zuleima

AU - Cattrell, Anna

AU - Conrod, Patricia

AU - Jia, Tianye

AU - Macare, Christine

AU - Mallik, Catherine

AU - Nymberg, Charlotte

AU - Reuter, Jan

AU - Ruggeri, Barbara

AU - Struve, Maren

AU - Topper, Lauren

PY - 2020/11/1

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N2 - 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.

AB - 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.

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DO - 10.1038/s41380-020-0822-5

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SN - 1359-4184

VL - 25

SP - 2648

EP - 2671

JO - Molecular Psychiatry

JF - Molecular Psychiatry

IS - 11

ER -

The IMAGEN study: a decade of imaging genetics in adolescents

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