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Articles by W. H Sommer
Total Records ( 2 ) for W. H Sommer
  J Treutlein , S Cichon , M Ridinger , N Wodarz , M Soyka , P Zill , W Maier , R Moessner , W Gaebel , N Dahmen , C Fehr , N Scherbaum , M Steffens , K. U Ludwig , J Frank , H. E Wichmann , S Schreiber , N Dragano , W. H Sommer , F Leonardi Essmann , A Lourdusamy , P Gebicke Haerter , T. F Wienker , P. F Sullivan , M. M Nothen , F Kiefer , R Spanagel , K Mann and M. Rietschel
 

Context  Alcohol dependence is a serious and common public health problem. It is well established that genetic factors play a major role in the development of this disorder. Identification of genes that contribute to alcohol dependence will improve our understanding of the mechanisms that underlie this disorder.

Objective  To identify susceptibility genes for alcohol dependence through a genome-wide association study (GWAS) and a follow-up study in a population of German male inpatients with an early age at onset.

Design  The GWAS tested 524 396 single-nucleotide polymorphisms (SNPs). All SNPs with P < 10–4 were subjected to the follow-up study. In addition, nominally significant SNPs from genes that had also shown expression changes in rat brains after long-term alcohol consumption were selected for the follow-up step.

Setting  Five university hospitals in southern and central Germany.

Participants  The GWAS included 487 male inpatients with alcohol dependence as defined by the DSM-IV and an age at onset younger than 28 years and 1358 population-based control individuals. The follow-up study included 1024 male inpatients and 996 age-matched male controls. All the participants were of German descent.

Main Outcome Measures  Significant association findings in the GWAS and follow-up study with the same alleles.

Results  The GWAS produced 121 SNPs with nominal P < 10–4. These, together with 19 additional SNPs from homologues of rat genes showing differential expression, were genotyped in the follow-up sample. Fifteen SNPs showed significant association with the same allele as in the GWAS. In the combined analysis, 2 closely linked intergenic SNPs met genome-wide significance (rs7590720, P = 9.72 x 10–9; rs1344694, P = 1.69 x 10–8). They are located on chromosome region 2q35, which has been implicated in linkage studies for alcohol phenotypes. Nine SNPs were located in genes, including the CDH13 and ADH1C genes, that have been reported to be associated with alcohol dependence.

Conclusions  This is the first GWAS and follow-up study to identify a genome-wide significant association in alcohol dependence. Further independent studies are required to confirm these findings.

  S. G Lindell , M. L Schwandt , H Sun , J. D Sparenborg , K Bjork , J. W Kasckow , W. H Sommer , D Goldman , J. D Higley , S. J Suomi , M Heilig and C. S. Barr
 

Context  Neuropeptide Y (NPY) counters stress and is involved in neuroadaptations that drive escalated alcohol drinking in rodents. In humans, low NPY expression predicts amygdala response and emotional reactivity. Genetic variation that affects the NPY system could moderate stress resilience and susceptibility to alcohol dependence.

Objective  To determine whether functional NPY variation influences behavioral adaptation to stress and alcohol consumption in a nonhuman primate model of early adversity (peer rearing).

Design  We sequenced the rhesus macaque NPY locus (rhNPY) and performed in silico analysis to identify functional variants. We performed gel shift assays using nuclear extract from testes, brain, and hypothalamus. Levels of NPY in cerebrospinal fluid were measured by radioimmunoassay, and messenger RNA levels were assessed in the amygdala using real-time polymerase chain reaction. Animals were exposed to repeated social separation stress and tested for individual differences in alcohol consumption. Animals were genotyped for –1002 T > G, and the data were analyzed using analysis of variance.

Setting  National Institutes of Health Animal Center.

Subjects  Ninety-six rhesus macaques.

Main Outcome Measure  Behavior arousal during social separation stress and ethanol consumption.

Results  The G allele altered binding of regulatory proteins in all nuclear extracts tested, and –1002 T > G resulted in lower levels of NPY expression in the amygdala. Macaques exposed to adversity had lower cerebrospinal fluid NPY levels and exhibited higher levels of arousal during stress, but only as a function of the G allele. We also found that stress-exposed G allele carriers consumed more alcohol and exhibited an escalation in intake over cycles of alcohol availability and deprivation.

Conclusions  Our results suggest a role for NPY promoter variation in the susceptibility to alcohol use disorders and point to NPY as a candidate for examining gene x environment interactions in humans.

 
 
 
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