Electronic Supplementary Material 6
Genetics and brain morphology
Lachlan T. Strike1*, Baptiste Couvy-Duchesne1, Narelle K. Hansell1, Gabriel Cuellar-Partida, Sarah E. Medland, Margaret J.
Wright
Lachlan T. Strike, Baptiste Couvy-Duchesne
Neuroimaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane QLD 4006, Australia
School of Psychology, University of Queensland, Brisbane QLD 4072, Australia
Centre for Advanced Imaging, University of Queensland, Brisbane QLD 4072, Australia
Narelle K. Hansell
Neuroimaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane QLD 4006, Australia
Gabriel Cuellar-Partida
Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane QLD 4006, Australia
Sarah E. Medland
Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane QLD 4006, Australia
Margaret J. Wright
Neuroimaging Genetics, QIMR Berghofer Medical Research Institute, Brisbane QLD 4006, Australia
School of Psychology, University of Queensland, Brisbane QLD 4072, Australia
1
*
LS, BCD and NH contributed equally to this work.
Corresponding author
Lachlan T. Strike
Lachlan.Strike@qimrberghofer.edu.au
Online Resource 6. GWAS on functional magnetic resonance imaging and magnetic resonance spectroscopy phenotypes
Authors
Phenotype
Discovery sample size
Replication sample
Sample Ethnicity
Genome –Wide
significant associationa
Replicationa
Potkin et al. (2009)
BOLD signal in the dorsolateral prefrontal
cortex during the probe condition
for a memory load of 3 items
FBIRN: 138 (64 SCZ, 74 HC)
NA
Mostly European
(80%)
No
NA
Baranzini et al. (2010)
Glutamate level
382 MS
NA
European
No
NA
Liu et al. (2010)
Amygdala activation during face
recognition paradigm
68 (39 BD, 29 HC)
NA
Mostly European
(84%)
No
No
Liu et al. (2011)
Brain serotonin transporter 5-HTT levels
in thalamus
55 (22HC, 16 BD, 17 MDD)
51
Mix / European
No
No
Brown et al. (2012)
Hyperactivated cortical regions during
face recognition paradigm
Negative faces: 246 (108 HC, 138
cases)
Positive faces: 284 (124 HC, 160
cases)
85 (non-independent
sample)
European / North
American Caucasian
No
Subject to cautionb
Ousdal et al. (2012)
Amygdala activation during face paradigm
TOP: 224 (97 HC, 51 SCZ, 64 BD, 12 DNS:100 HC
European / Mixed
3 SNP is high LD
No
other)
(50% European)
a
At the discovery stage the Genome-Wide significance threshold for one phenotype = 5.10-8. When several traits are tested a correction for multiple testing is required. When this step had been ignored we calculated
and used a threshold of 5.10-8/Ntrait (Bonferroni correction). A similar correction for multiple testing has been applied at the replication stage to control for the number of tests performed.
b
This study was greatly underpowered and suffers methodological limitations. The prior hypothesis (derived from the discovery analysis) contained a high rate of false positive (false discovery rate = 0.5). Nonindependence of the “replication sample” does not add much confidence in the final results being true positive.
AD Alzheimer’s disease; BD bipolar disorder; CSF cerebral spinal fluid; GM grey matter; HC healthy controls; MD major depressive disorder; MCI mild cognitive impairment, MS multiple sclerosis cases; P&AD
psychotic and affective disorder cases; SCZ schizophrenic cases; WMHI white matter hyperintensities.
References
Baranzini, S. E., Srinivasan, R., Khankhanian, P., Okuda, D. T., Nelson, S. J., Matthews, P.
M., et al. (2010). Genetic variation influences glutamate concentrations in brains of
patients with multiple sclerosis. Brain, 133(9), 2603-2611, doi:10.1093/brain/awq192.
Brown, A. A., Jensen, J., Nikolova, Y. S., Djurovic, S., Agartz, I., Server, A., et al. (2012).
Genetic variants affecting the neural processing of human facial expressions: evidence
using a genome-wide functional imaging approach. Transl Psychiatry, 2, e143,
doi:10.1038/tp.2012.67.
Liu, X., Akula, N., Skup, M., Brotman, M. A., Leibenluft, E., & McMahon, F. J. (2010). A
genome-wide association study of amygdala activation in youths with and without
bipolar disorder. J Am Acad Child Adolesc Psychiatry, 49(1), 33-41.
Liu, X., Cannon, D. M., Akula, N., Moya, P. R., Knudsen, G. M., Arentzen, T. E., et al.
(2011). A non-synonymous polymorphism in galactose mutarotase (GALM) is
associated with serotonin transporter binding potential in the human thalamus: results
of a genome-wide association study. Mol Psychiatry, 16(6), 584-585,
doi:10.1038/mp.2011.1.
Ousdal, O. T., Anand Brown, A., Jensen, J., Nakstad, P. H., Melle, I., Agartz, I., et al. (2012).
Associations between variants near a monoaminergic pathways gene (PHOX2B) and
amygdala reactivity: a genome-wide functional imaging study. Twin Res Hum Genet,
15(3), 273-285, doi:10.1017/thg.2012.5.
Potkin, S. G., Turner, J. A., Guffanti, G., Lakatos, A., Fallon, J. H., Nguyen, D. D., et al.
(2009). A genome-wide association study of schizophrenia using brain activation as a
quantitative phenotype. Schizophr Bull, 35(1), 96-108, doi:10.1093/schbul/sbn155.