scholarly journals Genomewide Gene-by-Sex Interaction Scans Identify ADGRV1 for Sex Differences in Opioid Dependent African Americans

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bao-Zhu Yang ◽  
Hang Zhou ◽  
Zhongshan Cheng ◽  
Henry R. Kranzler ◽  
Joel Gelernter

AbstractSex differences in opioid dependence (OD) are genetically influenced. We conducted genomewide gene-by-sex interaction scans for the DSM-IV diagnosis of OD in 8,387 African-American (AA) or European-American subjects (43.6% women; 4,715 OD subjects). Among AAs, 9 SNPs were genome-wide significant at ADGRV1 (adhesion G-protein-coupled receptor V1, lead-SNP rs2366929*(C/T), p = 1.5 × 10−9) for sex-different risk of OD, with the rs2366929*C-allele increasing OD risk only for men. The top co-expressions in brain were between ADGRV1 and GRIK2 in substantia nigra and medullary inferior olivary nucleus, and between ADGRV1 and EFHC2 in frontal cortex and putamen. Significant sex-differential ADGRV1 expression from GTEx was detected in breast (Bonferroni-corrected-p < 0.002) and in heart (p < 0.0125), with nominal significance identified in brain, thyroid, lung, and stomach (p < 0.05). ADGRV1 co-expression and disease-enrichment analysis identifying the top 10 diseases showed strikingly sexually dimorphic risks. The enrichment and transcriptome analyses provided convergent support that ADGRV1 exerts a sex-different effect on OD risk. This is the first study to identify genetic variants contributing to sex differences in OD. It shows that ADGRV1 contributes to OD risk only in AA men, a finding that warrants further study.

1985 ◽  
Vol 24 (7) ◽  
pp. 645-654 ◽  
Author(s):  
L.A. Barragan ◽  
N. Delhaye-Bouchaud ◽  
P. Laget

2018 ◽  
Vol 5 (1) ◽  
Author(s):  
Elan D. Louis ◽  
Daniel Trujillo Diaz ◽  
Sheng-Han Kuo ◽  
Shi-Rui Gan ◽  
Etty P. Cortes ◽  
...  

2008 ◽  
Vol 104 (5) ◽  
pp. 1351-1358 ◽  
Author(s):  
Jianguo Zhuang ◽  
Fadi Xu ◽  
Donald T. Frazier

Several studies have demonstrated that cerebellar deep nuclei, particularly the rostral fastigial nucleus (FNr), are involved in respiratory modulation. These nuclei receive inputs from the contralateral caudal inferior olivary nuclei of the medulla. The objectives of this study were to determine whether electrical and chemical activation of the vicinity of the caudal inferior olivary nuclei (vIOc) affected respiration and, if true, whether the FNr was involved in the vIOc stimulation-evoked ventilatory responses. Experiments were conducted in 30 anesthetized and spontaneously breathing rats. Our results showed that 1) electrical (25 or 100 μA at 10 or 20 Hz for 10 s) and chemical (1 or 100 mM, 25–50 nl N-methyl-d-aspartate) stimulation of the vIOc augmented ventilation predominantly via increasing tidal volume; 2) the responses to the electrical stimulation were almost eliminated by lesion of the contralateral FNr via microinjection of ibotenic acid; and 3) the respiratory responses to electrical stimulation in the vicinity of the rostral IO were 65–70% smaller compared with that evoked by vIOc stimulation. These findings strongly suggest that vIOc neurons play a significant role in modulation of respiratory activity, largely depending on their projections to the FNr.


1993 ◽  
Vol 70 (5) ◽  
pp. 2181-2186 ◽  
Author(s):  
I. Lampl ◽  
Y. Yarom

1. Subthreshold membrane potential oscillations have been observed in different types of CNS neurons. In this in vitro study, we examined the possible role of these oscillations by analyzing the responses of neurons from the inferior olivary nucleus to a combined stimulation of sine wave and synaptic potentials. 2. A nonlinear summation of the sine wave and the synaptic potential occurred in olivary neurons; a superlinear summation occurred when the synaptic potential was elicited at the trough of the sine wave or during the rising phase. On the other hand, a less than linear summation occurred when the synaptic potentials were evoked during the falling phase of the wave. 3. Significant changes in the delay of the synaptic responses were observed. As a result of these changes, the maximum amplitude of the response occurred at the peak of the sine wave, regardless of the exact time of stimulation. The output of the neuron was therefore synchronized with the sine wave and depended only partly on the input phase. 4. These data demonstrate that neurons from the inferior olivary nucleus are capable of operating as accurate synchronizing devices. Moreover, by affecting the delay line, they act as a logic gate that ensures that the information will be added to the system only at given times.


2015 ◽  
Vol 7 (2) ◽  
pp. 148-151 ◽  
Author(s):  
Emilio Franco-Macías ◽  
Florinda Roldán-Lora ◽  
Paula Martínez-Agregado ◽  
Nuria Cerdá-Fuertes ◽  
Francisco Moniche

A 21-year-old right-handed man developed progressive dysarthria and gait disturbance over 4 months (associated with intermittent hiccups). During that time, he also suffered from uveitis. A physical examination showed pseudobulbar and pyramidal signs and genital and oral ulcers. A brain MRI revealed an extensive lesion mainly located in the ventral pons, with an extension upwards to the midbrain. The inferior olivary nucleus also showed hyperintensity. After the treatment with intravenous methylprednisolone and pulses of cyclophosphamide, he improved. As observed on his MRI, his lesions also improved, except for an increase of the inferior olivary nucleus, consistent with hypertrophic olivary degeneration. Neuro-Behçet tropism for ventral brainstem explains the usual presentation with pyramidal syndrome. Hypertrophic olivary degeneration due to pons involvement could explain the hiccup attacks in a few known cases.


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