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. 2017 Feb;42(3):598-605.
doi: 10.1038/npp.2016.153. Epub 2016 Aug 17.

The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk Gene

Renato Polimanti  1 , Qian Wang  1   2 , Shashwath A Meda  3 , Krishna T Patel  3 , Godfrey D Pearlson  1   3   4 , Hongyu Zhao  2   5 , Lindsay A Farrer  6 , Henry R Kranzler  7 , Joel Gelernter  1   4   5
Affiliations

The Interplay Between Risky Sexual Behaviors and Alcohol Dependence: Genome-Wide Association and Neuroimaging Support for LHPP as a Risk Gene

Renato Polimanti et al. Neuropsychopharmacology. 2017 Feb.

Abstract

To identify genetic mechanisms involved in the interplay of risky sexual behaviors (RSBs) and alcohol dependence (AD), we conducted genome-wide gene-by-AD (GW-GxAD) analyses of RSB in 3924 alcohol-exposed and sexually experienced subjects. RSBs were defined as a score based on lifetime experiences of unprotected sex and multiple sexual partners. Diagnosis of lifetime AD was defined by DSM-IV criteria. To follow-up the genetic findings, functional magnetic resonance imaging analyses were conducted in an independent sample. A trans-population genome-wide significant signal was identified in LHPP (rs34997829; z=-5.573, p=2.51 × 10-8) in the GxAD analysis that also showed associations in the AD-stratified association analysis (AD z=-2.032 and non-AD z=4.903). The clinical relevance of the result was confirmed by the significant interaction between LHPP rs34997829 and AD with respect to self-reported sexually transmitted disease (STD; z=-2.809, p=4.97 × 10-3). The neuroimaging follow-up analysis of LHPP rs34997829 showed reduced power of the left superior frontal gyrus (t=-3.386, p=9.56 × 10-4) and increased power at the right amygdala (t=3.287, p=1.33 × 10-3) in the resting amplitude of low frequency fluctuations analysis; and reduced activation of the anterior cingulate region (t=-2.961, p=3.69 × 10-3) in the monetary incentive delay task. In conclusion, LHPP locus is associated to AD-RSB interaction; and with brain circuitries previously implicated in the inhibition of risky behavior and impulsiveness, emotional regulation, and impulse control/error monitoring. Thus, LHPP is a strong candidate to influence RSB and STD risk in the context of AD.

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Figures

Figure 1
Figure 1
Regional Manhattan plots of LHPP rs34997829 in the genome-wide gene-by-alcohol dependence (GW-GxAD) analyses of risky sexual behaviors (RSB) considering the trans-population meta-analysis (left), African-Americans (AAs; center), and European-Americans (EAs; right). There were no markers in either population (ie, African and European reference populations of the 1000 Genomes Project Phase 3) for which LHPP rs34997829 showed LD r2>0.6; therefore these figures appear comparatively sparse.
Figure 2
Figure 2
Association of LHPP rs34997829 with the power of left superior frontal gyrus and the right amygdala in the amplitude of low frequency fluctuations (ALFF) analysis (false discovery rate (FDR) q<0.1). A full color version of this figure is available at the Neuropsychopharmacology journal online.
Figure 3
Figure 3
Association of LHPP rs34997829 with the activation of anterior cingulate region in the monetary incentive delay (MID) task (false discovery rate (FDR) q<0.1). A full color version of this figure is available at the Neuropsychopharmacology journal online.
See this image and copyright information in PMC

References

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