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  Towards robust functional neuroimaging genetics of cognition

Udden, J., Hulten, A., Bendt, K., Mineroff, Z., Kucera, K. S., Vino, A., et al. (2019). Towards robust functional neuroimaging genetics of cognition. Journal of Neuroscience, 39(44), 8778-8787. doi:10.1523/JNEUROSCI.0888-19.2019.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0004-AB0D-E Version Permalink: http://hdl.handle.net/21.11116/0000-0004-F56D-E
Genre: Journal Article

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The Perils of Neuroimaging Genetics for Cognitive Traits (feature commentary)
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 Creators:
Udden, Julia1, 2, 3, Author              
Hulten, Annika1, 2, Author              
Bendt, Katarina3, Author
Mineroff, Zachary4, Author
Kucera, Katerina S.5, Author              
Vino, Arianna5, Author              
Fedorenko, Evelina4, 6, 7, Author
Hagoort, Peter1, 2, Author              
Fisher, Simon E.2, 5, Author              
Affiliations:
1Neurobiology of Language Department, MPI for Psycholinguistics, Max Planck Society, ou_792551              
2Donders Institute for Brain, Cognition and Behaviour, External Organizations, ou_55236              
3Stockholm University, Zweden, ou_persistent22              
4Brain and Cognitive Sciences Department, Massachusetts Institute of Technology, Cambridge, Massachusetts, MA, USA, ou_persistent22              
5Language and Genetics Department, MPI for Psycholinguistics, Max Planck Society, ou_792549              
6McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, MA, USA, ou_persistent22              
7Massachusetts General Hospital, Charlestown, Massachusetts MA, USA, ou_persistent22              

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 Abstract: A commonly held assumption in cognitive neuroscience is that, because measures of human brain function are closer to underlying biology than distal indices of behavior/cognition, they hold more promise for uncovering genetic pathways. Supporting this view is an influential fMRI-based study of sentence reading/listening by Pinel et al. (2012), who reported that common DNA variants in specific candidate genes were associated with altered neural activation in language-related regions of healthy individuals that carried them. In particular, different single-nucleotide polymorphisms (SNPs) of FOXP2 correlated with variation in task-based activation in left inferior frontal and precentral gyri, whereas a SNP at the KIAA0319/TTRAP/THEM2 locus was associated with variable functional asymmetry of the superior temporal sulcus. Here, we directly test each claim using a closely matched neuroimaging genetics approach in independent cohorts comprising 427 participants, four times larger than the original study of 94 participants. Despite demonstrating power to detect associations with substantially smaller effect sizes than those of the original report, we do not replicate any of the reported associations. Moreover, formal Bayesian analyses reveal substantial to strong evidence in support of the null hypothesis (no effect). We highlight key aspects of the original investigation, common to functional neuroimaging genetics studies, which could have yielded elevated false-positive rates. Genetic accounts of individual differences in cognitive functional neuroimaging are likely to be as complex as behavioral/cognitive tests, involving many common genetic variants, each of tiny effect. Reliable identification of true biological signals requires large sample sizes, power calculations, and validation in independent cohorts with equivalent paradigms. SIGNIFICANCE STATEMENT A pervasive idea in neuroscience is that neuroimaging-based measures of brain function, being closer to underlying neurobiology, are more amenable for uncovering links to genetics. This is a core assumption of prominent studies that associate common DNA variants with altered activations in task-based fMRI, despite using samples (10–100 people) that lack power for detecting the tiny effect sizes typical of genetically complex traits. Here, we test central findings from one of the most influential prior studies. Using matching paradigms and substantially larger samples, coupled to power calculations and formal Bayesian statistics, our data strongly refute the original findings. We demonstrate that neuroimaging genetics with task-based fMRI should be subject to the same rigorous standards as studies of other complex traits.

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Language(s): eng - English
 Dates: 2019-092019-10-30
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1523/JNEUROSCI.0888-19.2019
 Degree: -

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Title: Journal of Neuroscience
  Other : The Journal of Neuroscience: the Official Journal of the Society for Neuroscience
  Abbreviation : J. Neurosci.
Source Genre: Journal
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Publ. Info: Washington, DC : Society of Neuroscience
Pages: - Volume / Issue: 39 (44) Sequence Number: - Start / End Page: 8778 - 8787 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187_1