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Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression

Molecular Psychiatry volume 14, pages 621–630 (2009)Cite this article

Abstract

The HTR1A −1019C>G genotype was associated with major depression in the Utah population. Linkage analysis on Utah pedigrees with strong family histories of major depression including only cases with the HTR1A −1019G allele revealed a linkage peak on chromosome 10 (maximum HLOD=4.4). Sequencing of all known genes in the linkage region revealed disease-segregating single-nucleotide polymorphisms (SNPs) in LHPP. LHPP SNPs were also associated with major depression in both Utah and Ashkenazi populations. Consistent with the linkage evidence, LHPP associations depended on HTR1A genotype. Lhpp or a product of a collinear brain-specific transcript, therefore, may interact with Htr1a in the pathogenesis of major depression.

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Acknowledgements

We thank Drs James P Sullivan, Brian B Spear, Donald N Halbert and Jerry Lanchbury for the guidance and critical review of our work. This work was funded by Abbott Laboratories and Myriad Genetics. We are indebted to the individuals who agreed to participate in this study.

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Authors and Affiliations

  1. Myriad Genetics, Salt Lake City, UT, USA

    C D Neff, V Abkevich, Y Chen, J Potter, R Riley, C Davenport, J DeGrado Warren, S Jammulapati, A Gutin, M H Skolnick & D Shattuck

  2. Abbott Laboratories, Abbott Park, IL, USA

    J C L Packer, A Bhathena, W S Choi, P E Kroeger, R E Metzger & D A Katz

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  1. C D Neff
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Correspondence to D Shattuck or D A Katz.

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

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Neff, C., Abkevich, V., Packer, J. et al. Evidence for HTR1A and LHPP as interacting genetic risk factors in major depression. Mol Psychiatry 14, 621–630 (2009). https://doi.org/10.1038/mp.2008.8

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Keywords

  • genetic linkage
  • genetic association
  • major depression
  • serotonin receptor
  • epistasis

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