RESUMEN
BACKGROUND: Alcohol and tobacco use are heritable phenotypes. However, only a small number of common genetic variants have been identified, and common variants account for a modest proportion of the heritability. Therefore, this study aims to investigate the role of low-frequency and rare variants in alcohol and tobacco use. METHODS: We meta-analyzed ExomeChip association results from eight discovery cohorts and included 12,466 subjects and 7432 smokers in the analysis of alcohol consumption and tobacco use, respectively. The ExomeChip interrogates low-frequency and rare exonic variants, and in addition a small pool of common variants. We investigated top variants in an independent sample in which ICD-9 diagnoses of "alcoholism" (Nâ¯=â¯25,508) and "tobacco use disorder" (Nâ¯=â¯27,068) had been assessed. In addition to the single variant analysis, we performed gene-based, polygenic risk score (PRS), and pathway analyses. RESULTS: The meta-analysis did not yield exome-wide significant results. When we jointly analyzed our top results with the independent sample, no low-frequency or rare variants reached significance for alcohol consumption or tobacco use. However, two common variants that were present on the ExomeChip, rs16969968 (pâ¯=â¯2.39â¯×â¯10-7) and rs8034191 (pâ¯=â¯6.31â¯×â¯10-7) located in CHRNA5 and AGPHD1 at 15q25.1, showed evidence for association with tobacco use. DISCUSSION: Low-frequency and rare exonic variants with large effects do not play a major role in alcohol and tobacco use, nor does the aggregate effect of ExomeChip variants. However, our results confirmed the role of the CHRNA5-CHRNA3-CHRNB4 cluster of nicotinic acetylcholine receptor subunit genes in tobacco use.
Asunto(s)
Consumo de Bebidas Alcohólicas/genética , Exones/genética , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Uso de Tabaco/genética , Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/diagnóstico , Alcoholismo/epidemiología , Alcoholismo/genética , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Humanos , Masculino , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple/genética , Receptores Nicotínicos/genética , Factores de Riesgo , Uso de Tabaco/epidemiología , Tabaquismo/diagnóstico , Tabaquismo/genéticaRESUMEN
OBJECTIVE: Prayer is generally recognized as an important aspect of religiousness. Relatively few empiric studies examined the relation between prayer and depressive symptoms in later life, and findings so far are mixed. METHOD: Respondents, aged 60-91 years, participated in the third (N = 1,702) and fourth (N = 1,346) assessment cycles, with three-year intervals, of the Longitudinal Aging Study Amsterdam. Data were collected on frequency of prayer, perceived meaningfulness of prayer, religious affiliation, church attendance, salience of religion, demographics, and health variables. Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression Scale. RESULTS: In the total sample, there was no significant association between frequency of prayer and depressive symptoms. Among those who were not religiously affiliated, prayer was associated with higher levels of depressive symptoms. The results were particularly pronounced among nonaffiliated widowed respondents; odds ratio for praying daily associated with having Center for Epidemiologic Studies-Depression Scale scores of 16 and higher amounted to 3.59 (99% confidence interval: 1.01-11.79). At three-year follow up, prayer did not predict change of depressive symptoms. CONCLUSIONS: As secularization in Western Europe progresses, the current results suggest that clinical exploration of private religiousness among older patients remains relevant, also among people who seem to be less religious.
