Nurnberger JI, Jr.

References (5)

Title : A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks - Kapoor_2013_Hum.Genet_132_1141
Author(s) : Kapoor M , Wang JC , Wetherill L , Le N , Bertelsen S , Hinrichs AL , Budde J , Agrawal A , Bucholz K , Dick D , Harari O , Hesselbrock V , Kramer J , Nurnberger JI, Jr. , Rice J , Saccone NL , Schuckit M , Tischfield J , Porjesz B , Edenberg HJ , Bierut L , Foroud T , Goate A
Ref : Hum Genet , 132 :1141 , 2013
Abstract : Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 x 10(-6)) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 x 10(-7)), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 x 10(-7)) and PLCL1 genes (p = 4.1 x 10(-6)) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p </= 10(-4)) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 x 10(-3), 3 x 10(-6)), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.
ESTHER : Kapoor_2013_Hum.Genet_132_1141
PubMedSearch : Kapoor_2013_Hum.Genet_132_1141
PubMedID: 23743675

Title : A risk allele for nicotine dependence in CHRNA5 is a protective allele for cocaine dependence - Grucza_2008_Biol.Psychiatry_64_922
Author(s) : Grucza RA , Wang JC , Stitzel JA , Hinrichs AL , Saccone SF , Saccone NL , Bucholz KK , Cloninger CR , Neuman RJ , Budde JP , Fox L , Bertelsen S , Kramer J , Hesselbrock V , Tischfield J , Nurnberger JI, Jr. , Almasy L , Porjesz B , Kuperman S , Schuckit MA , Edenberg HJ , Rice JP , Goate AM , Bierut LJ
Ref : Biological Psychiatry , 64 :922 , 2008
Abstract : BACKGROUND: A nonsynonymous coding polymorphism, rs16969968, of the CHRNA5 gene that encodes the alpha-5 subunit of the nicotinic acetylcholine receptor (nAChR) has been found to be associated with nicotine dependence. The goal of this study was to examine the association of this variant with cocaine dependence.
METHODS: Genetic association analysis was performed in two independent samples of unrelated case and control subjects: 1) 504 European Americans participating in the Family Study on Cocaine Dependence (FSCD) and 2) 814 European Americans participating in the Collaborative Study on the Genetics of Alcoholism (COGA).
RESULTS: In the FSCD, there was a significant association between the CHRNA5 variant and cocaine dependence (odds ratio = .67 per allele, p = .0045, assuming an additive genetic model), but in the reverse direction compared with that previously observed for nicotine dependence. In multivariate analyses that controlled for the effects of nicotine dependence, both the protective effect for cocaine dependence and the previously documented risk effect for nicotine dependence were statistically significant. The protective effect for cocaine dependence was replicated in the COGA sample. In COGA, effect sizes for habitual smoking, a proxy phenotype for nicotine dependence, were consistent with those observed in FSCD.
CONCLUSIONS: The minor (A) allele of rs16969968, relative to the major G allele, appears to be both a risk factor for nicotine dependence and a protective factor for cocaine dependence. The biological plausibility of such a bidirectional association stems from the involvement of nAChRs with both excitatory and inhibitory modulation of dopamine-mediated reward pathways.
ESTHER : Grucza_2008_Biol.Psychiatry_64_922
PubMedSearch : Grucza_2008_Biol.Psychiatry_64_922
PubMedID: 18519132

Title : Effects of cholinesterase inhibitors on the secretion of beta-amyloid precursor protein in cell cultures - Lahiri_1997_Ann.N.Y.Acad.Sci_826_416
Author(s) : Lahiri DK , Farlow MR , Nurnberger JI, Jr. , Greig NH
Ref : Annals of the New York Academy of Sciences , 826 :416 , 1997
Abstract : One of the main characteristics of Alzheimer's disease (AD) is the cerebrovascular deposition of the amyloid beta-peptide (A beta), which is derived from a larger beta-amyloid precursor protein (beta APP). The majority of beta APP is processed by either a secretory of lysosomal/endosomal pathway. Carboxyl-truncated soluble derivatives of beta APP (sAPP) are generated by the proteolytic processing of full-length beta APP by either alpha- or beta-secretase enzyme. Our objective is to determine whether the processing of beta APP can be regulated by cholinesterase inhibitors, some of which were shown to produce a moderate improvement in memory and cognitive functions in patients with Alzheimer's disease. Here we have analyzed the levels of sAPP derivatives in cultured cells treated with different drugs by immunoblotting samples of conditioned media. The immunoreactive protein bands were developed by probing with the monoclonal antibody 22C11. Treating neuroblastoma, pheochromocytoma and fibroblast cells with high dose of either 3,4-diaminopyridine, metrifonate, or physostigmine did not inhibit the secretion of sAPP. Treating glioblastoma with either 3,4-diaminopyridine or metrifonate showed an increase in secretion of sAPP. However, treatment of cells with tacrine reduced release of sAPP in conditioned media of cell lines studied. The difference in action of metrifonate, physostigmine, and tacrine on beta APP is independent of their anticholinesterase activities. Our results suggests that noncatalytic functions of cholinesterase inhibitors can be utilized to alter the metabolism of beta APP, which might in turn affect the process of deposition of A beta, a key component of the cerebrovascular amyloid detected in AD.
ESTHER : Lahiri_1997_Ann.N.Y.Acad.Sci_826_416
PubMedSearch : Lahiri_1997_Ann.N.Y.Acad.Sci_826_416
PubMedID: 9329715

Title : Cholinergic regulation of mood and REM sleep: potential model and marker of vulnerability to affective disorder - Sitaram_1982_Am.J.Psychiatry_139_571
Author(s) : Sitaram N , Nurnberger JI, Jr. , Gershon ES , Gillin JC
Ref : Am J Psychiatry , 139 :571 , 1982
Abstract : To test the hypothesis that depression and REM sleep share common cholinergic mechanisms the authors administered arecoline 25 min after completion of the first REM period to 14 patients with remitted bipolar affective disorder, 15 normal controls, and 5 subjects with a personal or family history of affective disorder. The second REM period occurred significantly sooner in the remitted patients than in the normal controls. The patients also had a significantly higher density of eye movements during the first REM period and a higher percentage of REM sleep. The authors believe that increased cholinergic sensitivity and REM density may be biological markers of increased vulnerability to bipolar affective illness.
ESTHER : Sitaram_1982_Am.J.Psychiatry_139_571
PubMedSearch : Sitaram_1982_Am.J.Psychiatry_139_571
PubMedID: 7072840

Title : Hypersensitive Cholinergic Functioning in Primary Affective Illness -
Author(s) : Sitaram N , Moore AM , Vanskiver C , Blendy J , Nurnberger JI, Jr. , Gershon ES
Ref : Advances in Behavioral Biology , 25 :947 , 1981
PubMedID: