Original Article

Prefrontal gray matter volume mediates genetic risks for obesity

  • Molecular Psychiatry volume 22, pages 703710 (2017)
  • doi:10.1038/mp.2017.51
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Abstract

Genetic and neuroimaging research has identified neurobiological correlates of obesity. However, evidence for an integrated model of genetic risk and brain structural alterations in the pathophysiology of obesity is still absent. Here we investigated the relationship between polygenic risk for obesity, gray matter structure and body mass index (BMI) by the use of univariate and multivariate analyses in two large, independent cohorts (n=330 and n=347). Higher BMI and higher polygenic risk for obesity were significantly associated with medial prefrontal gray matter decrease, and prefrontal gray matter was further shown to significantly mediate the effect of polygenic risk for obesity on BMI in both samples. Building on this, the successful individualized prediction of BMI by means of multivariate pattern classification algorithms trained on whole-brain imaging data and external validations in the second cohort points to potential clinical applications of this imaging trait marker.

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Acknowledgements

The study was supported by grants from the German Research Foundation (DFG; Grants FOR 2107, DA1151/5-1 to UD, and SFB-TRR58, Project C09 to UD), and the Interdisciplinary Centre for Clinical Studies (IZKF, Grant Dan3/012/17 to UD). The BiDirect Study is supported by the German Federal Ministry of Education and Research (BMBF, Grants FKZ-01ER0816, FKZ-01ER1506 and FKZ-01ER1205).

Author contributions

Study concept and design: NO, RR, DG, KD, WH, VA, BTB, NK, KB and UD. Acquisition, analysis or interpretation of data: NO, RR, KD, AT, CK, HW, NK, BTB, KB, VA, HK and UD. Drafting of the manuscript: NO and UD. Critical revision of the manuscript for important intellectual content: RR, DG, CK, KD, WH, VA, AT, NK, AT, HW, BTB, KB, HK and UD. Statistical analysis: NO, RR, CK, DG and UD. Obtained funding: UD and KB. Administrative, technical or material support: RR, NO, DG, CK, KD, AT, NK, AT, HW, BTB, KB, VA, HK and UD. Study supervision: NO, RR, DG, UD, WH, HK, KB, BTB and VA.

Ethical statement

The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Declaration of Helsinki of 1975, as revised in 2008.

Author information

Affiliations

  1. Department of Psychiatry, University of Münster, Münster, Germany

    • N Opel
    • , R Redlich
    • , C Kaehler
    • , D Grotegerd
    • , K Dohm
    • , V Arolt
    •  & U Dannlowski
  2. Department of Mathematics and Computer Science, University of Münster, Münster, Germany

    • C Kaehler
  3. Department of Clinical Radiology, University of Münster, Münster, Germany

    • W Heindel
    •  & H Kugel
  4. Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia

    • A Thalamuthu
  5. Department of Psychiatry, University of Munich, Munich, Germany

    • N Koutsouleris
  6. Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany

    • A Teuber
    • , H Wersching
    •  & K Berger
  7. Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA, Australia

    • B T Baune

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Competing interests

V Arolt is a member of advisory boards and/or gave presentations for the following companies: Astra-Zeneca, Eli Lilly, Janssen-Organon, Lundbeck, Otsuka, Servier and Trommsdorff. These affiliations have no relevance to the work covered in the manuscript. The remaining authors declare no conflict of interest.

Corresponding author

Correspondence to U Dannlowski.

Supplementary information

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)