Despite twin studies showing that 50–70% of variation in DSM-IV cannabis dependence is attributable to heritable influences, little is known of specific genotypes that influence vulnerability to ...cannabis dependence. We conducted a genomewide association study of DSM-IV cannabis dependence. Association analyses of 708 DSM-IV cannabis dependent cases with 2,346 cannabis exposed nondependent controls was conducted using logistic regression in PLINK. None of the 948,142 SNPs met genomewide significance (p < E
−8
). The lowest p-values were obtained for polymorphisms on chromosome 17 (rs1019238 and rs1431318, p-values at E
−7
) in the
ANKFN1
gene. While replication is required, this study represents an important first step towards clarifying the biological underpinnings of cannabis dependence.
We sought to determine whether premenstrual mood symptoms exhibit familial aggregation in bipolar disorder or major depression pedigrees. Two thousand eight hundred seventy-six women were interviewed ...with the Diagnostic Interview for Genetic Studies as part of either the NIMH Genetics Initiative Bipolar Disorder Collaborative study or the Genetics of Early Onset Major Depression (GenRED) study and asked whether they had experienced severe mood symptoms premenstrually. In families with two or more female siblings with bipolar disorder (BP) or major depressive disorder (MDD), we examined the odds of having premenstrual mood symptoms given one or more siblings with these symptoms. For the GenRED MDD sample we also assessed the impact of personality as measured by the NEO-FFI. Premenstrual mood symptoms did not exhibit familial aggregation in families with BP or MDD. We unexpectedly found an association between high NEO openness scores and premenstrual mood symptoms, but neither this factor, nor NEO neuroticism influenced evidence for familial aggregation of symptoms. Limitations include the retrospective interview, the lack of data on premenstrual dysphoric disorder, and the inability to control for factors such as medication use.
Children of Alcoholics: Risk and Resilience Rice, Cara E; Dandreaux, Danielle; Handley, Elizabeth D ...
The prevention researcher,
11/2006, Volume:
13, Issue:
4
Journal Article
Peer reviewed
This article reviews the factors that influence the development of substance abuse and other negative outcomes among children of alcoholic parents (COAs). It reviews several pathways that may lead to ...the development of substance disorders for COAs, then explores protective factors that may decrease their risk for future negative outcomes.
Alcoholism is a complex disease with both genetic and environmental risk factors. To identify genes that affect the risk for alcoholism, we systematically ascertained and carefully assessed ...individuals in families with multiple alcoholics. Linkage and association analyses suggested that a region of chromosome 4p contained genes affecting a quantitative endophenotype, brain oscillations in the beta frequency range (13–28 Hz), and the risk for alcoholism. To identify the individual genes that affect these phenotypes, we performed linkage disequilibrium analyses of 69 single-nucleotide polymorphism (SNPs) within a cluster of four GABA
A
receptor genes,
GABRG1, GABRA2, GABRA4,
and
GABRB1,
at the center of the linked region. GABA
A
receptors mediate important effects of alcohol and also modulate beta frequencies. Thirty-one SNPs in
GABRA2,
but only 1 of the 20 SNPs in the flanking genes, showed significant association with alcoholism. Twenty-five of the
GABRA2
SNPs, but only one of the SNPs in the flanking genes, were associated with the brain oscillations in the beta frequency. The region of strongest association with alcohol dependence extended from intron 3 past the 3′ end of
GABRA2
; all 43 of the consecutive three-SNP haplotypes in this region of
GABRA2
were highly significant. A three-SNP haplotype was associated with alcoholism, with
P
=.000000022
. No coding differences were found between the high-risk and low-risk haplotypes, suggesting that the effect is mediated through gene regulation. The very strong association of
GABRA2
with both alcohol dependence and the beta frequency of the electroencephalogram, combined with biological evidence for a role of this gene in both phenotypes, suggest that
GABRA2
might influence susceptibility to alcohol dependence by modulating the level of neural excitation.
To determine normal cecal emptying curves for liquid- and solid-phase radiolabeled markers and to further define myoelectric patterns of the ileum, cecum, and colon in healthy ponies.
6 adult ponies.
...A cecal cannula and 12 bipolar Ag-AgCl recording electrodes were sutured to the ileum, cecum, and right ventral colon of the ponies. Radioisotopes, indium 111-labeled diethyltriaminepentaacetic acid (111In-DTPA) and technetium 99m (99mTc)-labeled sulfur colloid bound to egg albumen, were introduced through the cannula directly into the cecal body. Movement of these markers from the cecum was monitored by a gamma camera, and power exponential clearance curves were generated. Myoelectric data were collected before and after i.v. administration of isotonic saline (0.9% NaCl) solution, and were analyzed for spike burst (SB) rate, relative activity index, and mean burst duration. Myoelectric complexes were identified from observation of chart recordings or compressed, digitized data.
Clearance curves were generated for liquid (111In-DTPA)- and solid (99mTc)-phase markers. Marker types were not different with respect to lag phase, but liquid markers emptied at a slightly faster rate than did solids. Baseline values were calculated after saline solution administration for each of the myoelectric variables investigated. A relation between ileal, cecal, and colonic myoelectric activity was identified. Activity consistent with the previously described colonic migrating myoelectric complex in the pelvic flexure was identified in the right ventral colon.
Baseline data on normal cecal emptying was obtained; this technique could be used to evaluate the effect of postulated motility-modifying treatments used in equine practice.
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