Catechol-O-methyltransferase (COMT) is a major component of the metabolic pathways of neurotransmitters such as dopamine, adrenaline, and noradrenaline. The activity of COMT is known to vary within the population; it exists in common high-and low-activity forms that are determined by a Val → Met polymorphism at amino acid position 108/158 (in soluble or membranebound COMT). Recently, the low-activity allele was reported to contribute to the development of late-onset alcoholism in men. 1 The present study extends this study by utilizing a family-based association approach, and by including individuals with early-onset alcoholism. Although no significant transmission disequilibrium was found in the overall sample of 70 parent/offspring trios (TDT = 1.43, P = 0.23), we observed a preferential transmission of the low-activity allele to patients with an early onset of disease (n = 32, TDT = 4.83, P = 0.028). Our results provide further evidence for an involvement of the COMT low-activity allele in the development of alcoholism and demonstrate the need for further studies in large samples of alcoholic patients. Molecular Psychiatry (2001) 6, 109-111. Catechol-O-methyltransferase(COMT) is a biotransformation enzyme that inactivates biologically active or toxic catecholamines. It is a major component of the metabolic pathways of neurotransmitters such as noradrenaline, adrenaline and dopamine. 2 A single gene encodes membrane-bound (MB-COMT) and soluble (S-COMT) forms of the enzyme, which differ by a 50-amino acid hydrophobic N-terminal sequence that is present in the MB form. 3 A common genetic polymorphism in humans is associated with a three-to-fourfold variation in COMT enzyme activity and is also associated with individual variation in COMT thermal instability. [4][5][6] It was shown that this polymorphism is due to a G → A transition at codon 108 (158) of S-COMT (MB-COMT), that leads to a valine → methionine substitution. The valine → methionine substitution results in a low-activity allele. 6,7 In a global survey of populations, it was shown that frequencies of COMT high-and low-activity alleles vary greatly among ethnic groups. 8 Tiihonen and colleagues recently, 1 in this journal, reported a positive association between the COMT lowactivity allele and development of alcoholism. By applying a case-control design, they studied genotype and allele frequencies in a sample of 123 Finnish male alcoholics with late onset (over 25 years) and two independent sets of controls (3140 Finnish blood donors and 267 race-and gender-matched controls). The lowactivity allele was found to increase the risk for alcoholism, with an odds ratio of 2.51 (P = 0.006) for individuals homozygous for the low-activity allele vs those homozygous for the high-activity allele. Further support for a role of the COMT low-activity allele in drinking behavior was obtained in a population sample of 896 middle-aged Finnish men: men homozygous for the low-activity allele reported 27% higher weekly alcohol consumption compared with men from the two ot...

A search for the decays of the Higgs and Z bosons to a ϕ meson and a photon is performed with a pp collision data sample corresponding to an integrated luminosity of 2.7  fb^{-1} collected at sqrt[s]=13  TeV with the ATLAS detector at the LHC. No significant excess of events is observed above the background, and 95% confidence level upper limits on the branching fractions of the Higgs and Z boson decays to ϕγ of 1.4×10^{-3} and 8.3×10^{-6}, respectively, are obtained.

Dopaminergic abnormalities are implicated in the pathogenesis of substance abuse. 1 Recently, two reports have been published suggesting an association between opioid dependence and presence of long alleles of the dopamine D 4 receptor (DRD4) gene exon III VNTR. 2,3 We have attempted to replicate this finding using a two-tiered strategy employing independent case-control and family-based association samples. Our study was possibly the largest candidate gene association study to date on opioid dependence in a sample of 815 subjects, 396 of whom were patients. We found long alleles of the DRD4 exon III VNTR in similar frequency among 285 heroin addicts and 197 controls. Furthermore, no preferential transmission of long alleles to affected offspring was observed in a sample of 111 patients and their parents. Our results, therefore, do not support the hypothesis that alleles of the DRD4 exon III VNTR are susceptibility factors for opioid dependence in man. Molecular Psychiatry (2000) 5, 101-104.Although social and cultural influences are clearly important, family, twin and adoption studies indicate that genes contribute significantly to substance abuse, 4-6 including addiction to alcohol, cocaine and opioids. In search for genetic factors of opioid dependence, two recent case-control association studies have implicated the DRD4 exon III VNTR in the development of disease. 2,3 The study by Kotler et al 2 investigated the exon III VNTR in 141 male opioid-dependent subjects and 110 male control subjects from Israel, and found a significant excess of the 7-repeat allele, with an odds ratio of 3.06 (95% CI 1.38-4.35). Li et al 3 studied a Chinese sample of 121 heroin-dependent subjects and 154 controls. While the 7-repeat allele is extremely rare in Chinese populations and was only observed in two patients, dividing the VNTR alleles into 'long' (5-7 repeats) and 'short' (2-4 repeats) alleles showed a significant excess of long alleles in the patient group, with an odds ratio of 2.30 (95% CI 1.07-4.93). These observations clearly suggest a causal contribution of genetic variation in the DRD4 to the development of opioid dependence. In the present study, we have attempted to replicate this finding by genotyping DNA samples from 285 heroin addicts and 197 controls. Since a major flaw of case-control association studies is the problem of undetected population stratification, we also applied a family-based association study design by genotyping an independent sample of 111 heroin addicts and their parents to examine preferential transmission of alleles to affected offspring.The distributions of genotype and allele frequencies of the DRD4 exon III VNTR in patients and controls are shown in Tables 1 and 2. There were no significant differences between patients and controls in the frequency of the 7-repeat allele ( 2 = 2.444; df = 1; P = 0.188) nor in any of the other alleles (Table 2). At least one 7-repeat allele was found in 35.1% of heroindependent subjects and 27.4% of controls ( 2 = 3.157; df = 1; P = 0.076). Moreover, pat...

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