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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

Molecular Psychiatry volume 16, pages 584–585 (2011)Cite this article

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Positron emission tomography (PET) imaging using the tracer [11C]DASB is a sensitive and noninvasive technique for measuring brain serotonin transporter (5-HTT) levels in vivo.1 Previously, Cannon et al. found that 5-HTT levels were increased in thalamus, striatum, insular and cingulate cortices in unmedicated, depressed subjects with major depressive disorder2 or bipolar disorder.3 To explore this potential biomarker for mood disorders, we undertook a proof-of-principle genome-wide association study (GWAS).

5-HTT levels, measured as [11C]DASB-binding potential (BPND), were assessed in six brain regions-of-interest (ROIs). Healthy (n=22) and unmedicated participants diagnosed with bipolar disorder (n=16) or major depressive disorder (n=17), aged 18–48 years (mean±s.d., 34±9 years) underwent PET scanning with [11C]DASB. Subject ascertainment, PET scanning and analysis were described previously.2, 3 DNA was extracted from peripheral blood and genotyped on the Illumina Human-1 SNP array (Illumina, San Diego, CA, USA). Genotypes were analyzed using BeadStudio v3.0 (Illumina). Data were filtered for minor allele frequencies <1%, missing genotype rates >8%, Hardy–Weinberg equilibrium P-values <0.05, gender mismatch and hidden relatedness. A total of 93 427 single-nucleotide polymorphisms (SNPs) passed all quality control filters for all of the ROIs tested. Association analysis was performed by linear regression in PLINK4 (v1.02), with three covariates to control for ancestry. Genomic control lambda values were all <1.05, indicating good control of confounding factors.

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Acknowledgements

This research is funded by the NIMH Intramural Research Program.

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Author notes

  1. W C Drevets and F J McMahon: These senior authors contributed equally to this paper.

Authors and Affiliations

  1. Genetics of Mood and Anxiety Disorders Section, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    X Liu, N Akula, J Steele, G Laje & F J McMahon

  2. Section on Neuroimaging in Mood and Anxiety Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    D M Cannon & W C Drevets

  3. Department of Psychiatry, Clinical Neuroimaging Laboratory, National University of Ireland Galway, Galway, Ireland

    D M Cannon

  4. Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA

    P R Moya

  5. Center for Integrated Molecular Brain Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

    G M Knudsen & T E Arentzen

  6. Department of Psychiatry, Laureate Institute for Brain Research, University of Oklahoma College of Medicine, Tulsa, OK, USA

    W C Drevets

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  1. X Liu
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  2. D M Cannon
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  10. F J McMahon
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Correspondence to X Liu.

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Liu, X., Cannon, D., Akula, N. et al. 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, 584–585 (2011). https://doi.org/10.1038/mp.2011.1

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