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1.
Twin Res Hum Genet ; : 1-10, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31640839

RESUMO

This review offers an update on research conducted with FinnTwin12 (FT12), the youngest of the three Finnish Twin Cohorts. FT12 was designed as a two-stage study. In the first stage, we conducted multiwave questionnaire research enrolling all eligible twins born in Finland during 1983-1987 along with their biological parents. In stage 2, we intensively studied a subset of these twins with in-school assessments at age 12 and semistructured poly-diagnostic interviews at age 14. At baseline, parents of intensively studied twins were administered the adult version of the interview. Laboratory studies with repeat interviews, neuropsychological tests, and collection of DNA were made of intensively studied twins during follow-up in early adulthood. The basic aim of the FT12 study design was to obtain information on individual, familial and school/neighborhood risks for substance use/abuse prior to the onset of regular tobacco and alcohol use and then track trajectories of use and abuse and their consequences into adulthood. But the longitudinal assessments were not narrowly limited to this basic aim, and with multiwave, multirater assessments from ages 11 to 12, the study has created a richly informative data set for analyses of gene-environment interactions of both candidate genes and genomewide measures with measured risk-relevant environments. Because 25 years have elapsed since the start of the study, we are planning a fifth-wave follow-up assessment.

2.
Twin Res Hum Genet ; 22(4): 240-254, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31462340

RESUMO

The older Finnish Twin Cohort (FTC) was established in 1974. The baseline survey was in 1975, with two follow-up health surveys in 1981 and 1990. The fourth wave of assessments was done in three parts, with a questionnaire study of twins born during 1945-1957 in 2011-2012, while older twins were interviewed and screened for dementia in two time periods, between 1999 and 2007 for twins born before 1938 and between 2013 and 2017 for twins born in 1938-1944. The content of these wave 4 assessments is described and some initial results are described. In addition, we have invited twin-pairs, based on response to the cohortwide surveys, to participate in detailed in-person studies; these are described briefly together with key results. We also review other projects based on the older FTC and provide information on the biobanking of biosamples and related phenotypes.

3.
Epigenomics ; 11(13): 1469-1486, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31466478

RESUMO

Aim: Smoking strongly influences DNA methylation, with current and never smokers exhibiting different methylation profiles. Methods: To advance the practical applicability of the smoking-associated methylation signals, we used machine learning methodology to train a classifier for smoking status prediction. Results: We show the prediction performance of our classifier on three independent whole-blood datasets demonstrating its robustness and global applicability. Furthermore, we examine the reasons for biologically meaningful misclassifications through comprehensive phenotypic evaluation. Conclusion: The major contribution of our classifier is its global applicability without a need for users to determine a threshold value for each dataset to predict the smoking status. We provide an R package, EpiSmokEr (Epigenetic Smoking status Estimator), facilitating the use of our classifier to predict smoking status in future studies.

4.
Nicotine Tob Res ; 2019 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-31294817

RESUMO

INTRODUCTION: FTND (FagerstrÓ§m test for nicotine dependence) and TTFC (time to smoke first cigarette in the morning) are common measures of nicotine dependence (ND). However, genome-wide meta-analysis for these phenotypes has not been reported. METHODS: Genome-wide meta-analyses for FTND (N = 19,431) and TTFC (N = 18,567) phenotypes were conducted for adult smokers of European ancestry from 14 independent cohorts. RESULTS: We found that SORBS2 on 4q35 (p = 4.05 × 10-8), BG182718 on 11q22 (p = 1.02 × 10-8), and AA333164 on 14q21 (p = 4.11 × 10-9) were associated with TTFC phenotype. We attempted replication of leading candidates with independent samples (FTND, N = 7010 and TTFC, N = 10 061), however, due to limited power of the replication samples, the replication of these new loci did not reach significance. In gene-based analyses, COPB2 was found associated with FTND phenotype, and TFCP2L1, RELN, and INO80C were associated with TTFC phenotype. In pathway and network analyses, we found that the interconnected interactions among the endocytosis, regulation of actin cytoskeleton, axon guidance, MAPK signaling, and chemokine signaling pathways were involved in ND. CONCLUSIONS: Our analyses identified several promising candidates for both FTND and TTFC phenotypes, and further verification of these candidates was necessary. Candidates supported by both FTND and TTFC (CHRNA4, THSD7B, RBFOX1, and ZNF804A) were associated with addiction to alcohol, cocaine, and heroin, and were associated with autism and schizophrenia. We also identified novel pathways involved in cigarette smoking. The pathway interactions highlighted the importance of receptor recycling and internalization in ND. IMPLICATIONS: Understanding the genetic architecture of cigarette smoking and ND is critical to develop effective prevention and treatment. Our study identified novel candidates and biological pathways involved in FTND and TTFC phenotypes, and this will facilitate further investigation of these candidates and pathways.

5.
Drug Alcohol Depend ; 200: 64-70, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31100637

RESUMO

BACKGROUND: Longitudinal studies enhance understanding of the complex reciprocal relationship between smoking and depression from adolescence to young adulthood. Examining bi-directional associations between cigarette smoking and depressive symptoms in a genetically informative twin design can help to understand whether the associations are independent of shared genetic and environmental factors. METHODS: We analyzed longitudinal data on smoking and depressive symptoms in twins participating in the adolescent (mean age 17.5) and young adult (mean age 21.9) surveys of the FinnTwin12 study (maximum N = 2,954 individuals; 1,154 twin pairs). At both waves, self-reported depressive symptoms, assessed with the 10-item version of the General Behavior Inventory (GBI), and smoking status were analyzed. The bi-directional associations were first studied among individuals and then within monozygotic and dizygotic twin pairs. RESULTS: When adjusted for multiple covariates and baseline depressive symptoms, daily smokers at age 17 had higher depressive symptom scores at age 22 than never smokers (Incidence Rate Ratio = 1.17, 95% CI: 1.03-1.33). Similarly, when adjusted for covariates and baseline smoking, higher score in GBI at age 17 was associated with an increased likelihood of being a non-daily (Relative Risk Ratio (RRR) = 1.06, 95% CI: 1.01-1.11) or daily (RRR = 1.05, 95% CI: 1.00-1.10) smoker at age 22. No associations were found in within-pair analyses, suggesting that the individual-level association is explained by shared familial liabilities. CONCLUSION: During the developmental period from adolescence to adulthood, cigarette smoking and depressive symptoms are reciprocally associated. However, these associations are confounded by shared genetic and other familial liabilities.

6.
Prev Sci ; 20(7): 1021-1030, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31069603

RESUMO

Longitudinal, genetically informative studies of the association between cigarette smoking and depressive symptoms among adolescents are limited. We examined the longitudinal association of cigarette smoking with subsequent depressive symptoms during adolescence in a Finnish twin cohort. We used prospective data from the population-based FinnTwin12 study (maximum N = 4152 individuals, 1910 twin pairs). Current smoking status and a number of lifetime cigarettes smoked were assessed at the age of 14 and depressive symptoms at the age of 17. Negative binomial regression was conducted to model the association between smoking behavior and subsequent depressive symptoms among individuals, and within-pair analyses were conducted to control for unmeasured familial confounding. Analyses were adjusted for age, sex, school grades, drinking alcohol to intoxication, health status, family structure, parental education, and smoking, as well as for pre-existing depressiveness. The results of the individual-level analyses showed that cigarette smoking at the age of 14 predicted depressive symptoms at the age of 17. Compared to never smokers, those who had smoked over 50 cigarettes (incidence rate ratio, IRR = 1.43, 95% CI 1.28-1.60) and regular smokers (IRR = 1.46, 95% CI 1.32-1.62) had higher depression scores. The associations were attenuated when adjusted for measured covariates and further reduced in within-pair analyses. In the within-pair results, the estimates were lower within monozygotic (MZ) pairs compared to dizygotic (DZ) pairs, suggesting that shared genetic factors contribute to the associations observed in individual-based analyses. Thus, we conclude that cigarette smoking is associated with subsequent depressive symptoms during adolescence, but the association is not independent of measured confounding factors and shared genetic influences.

7.
Scand J Public Health ; : 1403494819828868, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30973058

RESUMO

AIMS: Swedish smokeless tobacco (snus) is a lower-risk tobacco product than cigarette smoking for individuals. However, the public health impact of snus use is less well studied. Critically, it is uncertain whether use of snus leads to the onset of smoking. This study aimed to investigate prospectively the association between snus experimentation in late adolescence and daily cigarette smoking in early adulthood among Finnish young men. METHODS: Data were obtained from 1090 young men within the population-based FinnTwin12 cohort. At baseline (mean age 17 years), we assessed lifetime use of cigarettes and snus, plus other potential predictors of cigarette smoking. At follow-up (mean age 24 years), participants were categorized according to their current smoking status. The final analyses were conducted among 375 young men who were never smokers at baseline with adequate data on follow-up smoking status and other potential predictors of cigarette smoking. RESULTS: Age-adjusted logistic regressions showed an increased risk of becoming a daily smoker at follow-up among those participants who had at least tried snus but had never smoked cigarettes at baseline (odds ratio (OR) 6.48, 95% confidence interval (CI) 2.02-20.7), compared with those who had never used snus. When additionally adjusted for monthly alcohol intoxication, maternal smoking, and peer drug use, the association between snus experimentation and later daily cigarette smoking was attenuated, but remained significant (OR 3.94, 95% CI 1.22-12.7). CONCLUSIONS: Our data support the proposition that snus experimentation during late adolescence is longitudinally associated with daily cigarette smoking in early adulthood. Although a causal association cannot be inferred with certainty, snus experimentation might constitute an indicator of the propensity to proceed to regular snus use and initiation of use of other tobacco or nicotine products.

8.
Clin Epigenetics ; 11(1): 1, 2019 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-30611298

RESUMO

BACKGROUND: DNA methylation alteration extensively associates with smoking and is a plausible link between smoking and adverse health. We examined the association between epigenome-wide DNA methylation and serum cotinine levels as a proxy of nicotine exposure and smoking quantity, assessed the role of SNPs in these associations, and evaluated molecular mediation by methylation in a sample of biochemically verified current smokers (N = 310). RESULTS: DNA methylation at 50 CpG sites was associated (FDR < 0.05) with cotinine levels, 17 of which are novel associations. As cotinine levels are influenced not only by nicotine intake but also by CYP2A6-mediated nicotine metabolism rate, we performed secondary analyses adjusting for genetic risk score of nicotine metabolism rate and identified five additional novel associations. We further assessed the potential role of genetic variants in the detected association between methylation and cotinine levels observing 124 cis and 3898 trans methylation quantitative trait loci (meQTLs). Nineteen of these SNPs were also associated with cotinine levels (FDR < 0.05). Further, at seven CpG sites, we observed a trend (P < 0.05) that altered DNA methylation mediates the effect of SNPs on nicotine exposure rather than a direct consequence of smoking. Finally, we performed replication of our findings in two independent cohorts of biochemically verified smokers (N = 450 and N = 79). CONCLUSIONS: Using cotinine, a biomarker of nicotine exposure, we replicated and extended identification of novel epigenetic associations in smoking-related genes. We also demonstrated that DNA methylation in some of the identified loci is driven by the underlying genotype and may mediate the causal effect of genotype on cotinine levels.


Assuntos
Cotinina/sangue , Metilação de DNA , Epigenômica/métodos , Polimorfismo de Nucleotídeo Único , Fumar/genética , Adulto , Idoso , Ilhas de CpG , Citocromo P-450 CYP2A6/genética , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Adulto Jovem
9.
Nicotine Tob Res ; 2018 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-30329132

RESUMO

Introduction: Brain derived neurotrophic factor (BDNF) is a growth factor in the central nervous system. There is evidence for the involvement of BDNF in addictions and mental disorders. We aimed to replicate the earlier reported association of a functional genetic variant of BDNF with smoking initiation (SI) using a large population-based sample, and to test whether the association is independent of depression. Methods: Our sample was drawn from the Finnish population-based FINRISK Surveys conducted in 1992, 1997, 2002 and 2007. We had non-missing data on the genotype BDNF Val66Met (G/A) variant (rs6265) and self-reported never (n=10,619) versus ever (n=16,028) smoking among 26,647 adults aged 25-74 years. The association between BDNF Val66Met and SI was modeled using logistic regression adjusted for age and sex, and in secondary analyses also for depression. Depression was defined as self-reported depression diagnosed or treated by physician during the past year. Results: The sex and age adjusted analysis confirmed that the major (Val) allele increased the risk of being a lifetime ever smoker (per allele OR=1.07; 95%CI 1.01, 1.12; p=0.01). When depression, which itself was significantly associated with SI (OR=1.58; 95%CI 1.37, 1.82; p<0.001), was added to the model, the association of the gene with SI remained significant (per allele OR=1.06; 95%CI 1.01, 1.12; p=0.01). Exclusion of depressed individuals did not change the results (OR=1.06; 95%CI 1.01, 1.12; p=0.02). Conclusions: In a Finnish population sample we replicated the earlier reported association of BDNF Val66Met with smoking initiation. Our data further suggest that this association is independent of depression.

10.
Artigo em Inglês | MEDLINE | ID: mdl-30019148

RESUMO

Modestly prevalent in the general population (~ 4%), but highly prevalent in prison populations (> 40%), the diagnosis of antisocial personality disorder (ASPD) involves aggression as one of several possible criteria. Using multiple informants, we aimed to determine if general aggression, as well as direct and indirect subtypes, assessed in early adolescence (ages 12, 14) predict young adulthood ASPD in a population-based sample. Using data from a Finnish population-based longitudinal twin cohort study with psychiatric interviews available at age 22 (N = 1347), we obtained DSM-IV-based ASPD diagnoses. Aggression measures from ages 12 (parental and teacher ratings) and 14 (teacher, self, and co-twin ratings) were used to calculate odds ratios (OR) of ASPD from logistic regression models and the area under the curve (AUC) from receiver operating characteristic curve analysis. Analyses were adjusted for sex, age, and family structure. All informants' aggression ratings were significant (p < 0.05) predictors of ASPD (OR range 1.3-1.8; AUC range 0.65-0.72). Correlations between informants ranged from 0.13 to 0.33. Models including two or more aggression ratings, particularly age 14 teacher and self ratings, more accurately predicted ASPD (AUC: 0.80; 95% confidence interval 0.73-0.87). Direct aggression rated by all informants significantly predicted ASPD (OR range 1.4-1.9), whereas only self-rated indirect aggression was significantly associated with ASPD (OR = 1.4). Across different informants, general and direct aggression at ages 12 and 14 predicted ASPD in a population-based sample. Psychiatric, social, and parenting interventions for ASPD prevention should focus on children and adolescents with high aggression levels, with an aim to gather information from multiple informants.

11.
Addiction ; 113(11): 2073-2086, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30003630

RESUMO

BACKGROUND AND AIMS: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. METHODS: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. RESULTS: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2  > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. CONCLUSION: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

12.
Psychol Med ; : 1-9, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29886849

RESUMO

BACKGROUND: Maternal smoking during pregnancy (MSDP) has been linked to offspring's externalizing problems. It has been argued that socio-demographic factors (e.g. maternal age and education), co-occurring environmental risk factors, or pleiotropic genetic effects may account for the association between MSDP and later outcomes. This study provides a comprehensive investigation of the association between MSDP and a single harmonized component of externalizing: aggressive behaviour, measured throughout childhood and adolescence. METHODS: Data came from four prospective twin cohorts - Twins Early Development Study, Netherlands Twin Register, Childhood and Adolescent Twin Study of Sweden, and FinnTwin12 study - who collaborate in the EU-ACTION consortium. Data from 30 708 unrelated individuals were analysed. Based on item level data, a harmonized measure of aggression was created at ages 9-10; 12; 14-15 and 16-18. RESULTS: MSDP predicted aggression in childhood and adolescence. A meta-analysis across the four samples found the independent effect of MSDP to be 0.4% (r = 0.066), this remained consistent when analyses were performed separately by sex. All other perinatal factors combined explained 1.1% of the variance in aggression across all ages and samples (r = 0.112). Paternal smoking and aggressive parenting strategies did not account for the MSDP-aggression association, consistent with the hypothesis of a small direct link between MSDP and aggression. CONCLUSIONS: Perinatal factors, including MSDP, account for a small portion of the variance in aggression in childhood and adolescence. Later experiences may play a greater role in shaping adolescents' aggressive behaviour.

13.
Int J Equity Health ; 17(1): 56, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29728104

RESUMO

BACKGROUND: Cervical cancer is currently ranked as the fourth commonly diagnosed cancer in women globally. A higher incidence has been reported in low- and-middle-income countries, and the disease poses significant public health challenges. Evidence suggests that this disease is preventable by means of regular screening using the Papanicolaou (Pap) test. However, limited knowledge exists about disparities in cervical screening participation among immigrants compared with non-immigrants, in countries with universal cervical screening programmes. We aimed to examine disparities in cervical screening participation among women of Russian, Somali, and Kurdish, origin in Finland, comparing them with the general Finnish population (Finns). We controlled for differences in several socio-demographic and health-related variables as potential confounders. METHODS: We employed data from the Finnish Migrant Health and Well-being Study 2010-2012 and the National Health 2011 Survey. Data collection involved face-to-face interviews. Data on screening participation in the previous five years from women aged 29-60 were available from 537 immigrants (257 Russians, 113 Somalis, 167 Kurds) and from 436 Finns. For statistical analyses, we used multiple logistic regression. RESULTS: Age-adjusted screening participation rates were as follows: Russians 79% (95% CI 72.9-84.4), Somalis 41% (95% CI 31.4-50.1), and Kurds 64% (95% CI 57.2-70.8), compared with 94% (95% CI 91.4-95.9) among Finns. After additionally adjusting for socio-demographic and health-related confounders, all the immigrant groups showed a significantly lower likelihood of screening participation when compared with Finns. The Odds Ratios were as follows: Russians 0.32 (95% CI 0.18-0.58), Somalis 0.10 (95% CI 0.04-0.23), and Kurds 0.17 (95% CI 0.09-0.35). However, when additionally accounting for country of origin-confounder interactions, such differences were attenuated. CONCLUSIONS: Our results indicate disparities in screening participation among these immigrants and a lower likelihood of screening participation compared with the general Finnish population. To improve equity in cervical cancer screening participation, appropriate culturally tailored intervention programmes for each immigrant group might be beneficial.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Emigrantes e Imigrantes/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Teste de Papanicolaou/estatística & dados numéricos , Adulto , Feminino , Finlândia/epidemiologia , Humanos , Irã (Geográfico)/etnologia , Modelos Logísticos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Federação Russa/etnologia , Somália/etnologia , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem
14.
Eur Child Adolesc Psychiatry ; 27(9): 1105-1121, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29845340

RESUMO

Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16 years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.


Assuntos
Sintomas Afetivos/psicologia , Agressão/psicologia , Transtornos do Comportamento Infantil/psicologia , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino
15.
Addict Biol ; 2018 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-29532581

RESUMO

The heritability of nicotine dependence based on family studies is substantial. Nevertheless, knowledge of the underlying genetic architecture remains meager. Our aim was to identify novel genetic variants responsible for interindividual differences in smoking behavior. We performed a genome-wide association study on 1715 ever smokers ascertained from the population-based Finnish Twin Cohort enriched for heavy smoking. Data imputation used the 1000 Genomes Phase I reference panel together with a whole genome sequence-based Finnish reference panel. We analyzed three measures of nicotine addiction-smoking quantity, nicotine dependence and nicotine withdrawal. We annotated all genome-wide significant SNPs for their functional potential. First, we detected genome-wide significant association on 16p12 with smoking quantity (P = 8.5 × 10-9 ), near CLEC19A. The lead-SNP stands 22 kb from a binding site for NF-κB transcription factors, which play a role in the neurotrophin signaling pathway. However, the signal was not replicated in an independent Finnish population-based sample, FINRISK (n = 6763). Second, nicotine withdrawal showed association on 2q21 in an intron of TMEM163 (P = 2.1 × 10-9 ), and on 11p15 (P = 6.6 × 10-8 ) in an intron of AP2A2, and P = 4.2 × 10-7 for a missense variant in MUC6, both involved in the neurotrophin signaling pathway). Third, association was detected on 3p22.3 for maximum number of cigarettes smoked per day (P = 3.1 × 10-8 ) near STAC. Associating CLEC19A and TMEM163 SNPs were annotated to influence gene expression or methylation. The neurotrophin signaling pathway has previously been associated with smoking behavior. Our findings further support the role in nicotine addiction.

16.
Dev Psychopathol ; 30(1): 79-92, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28424107

RESUMO

Early maturation, indexed by pubertal development (PD), has been associated with earlier initiation and greater frequency of adolescent substance use, but this relationship may be biased by confounding factors and effects that change across development. Using a population-based Finnish twin sample (N = 3,632 individuals), we conducted twin modeling and multilevel structural equation modeling of the relationship between PD and substance use at ages 12-22. Shared environmental factors contributed to early PD and heavier substance use for females. Biological father absence was associated with early PD for boys but not girls, and did not account for the relationship between PD and substance use. The association between early PD and heavier substance use was partially due to between-family confounds, although early PD appeared to qualitatively alter long-term trajectories for some substances (nicotine), but not others (alcohol). Mediation by peer and parental factors did not explain this relationship within families. However, higher peer substance use and lower parental monitoring were themselves associated with heavier substance use, strengthening the existing evidence for these factors as targets for prevention/intervention efforts. Early maturation was not supported as a robust determinant of alcohol use trajectories in adolescence and young adulthood, but may require longer term follow-up. Subtle effects of early PD on nicotine and illicit drug use trajectories throughout adolescence and adulthood merit further investigation.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Poder Familiar , Grupo Associado , Meio Social , Transtornos Relacionados ao Uso de Substâncias/etiologia , Gêmeos , Adolescente , Consumo de Bebidas Alcoólicas/psicologia , Criança , Doenças em Gêmeos , Feminino , Finlândia , Humanos , Estudos Longitudinais , Masculino , Transtornos Relacionados ao Uso de Substâncias/genética , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto Jovem
17.
Addict Behav ; 79: 32-38, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29245024

RESUMO

BACKGROUND: Developmental relationships between tobacco use and suicide-related behaviors (SRB) remain unclear. Our objective was to investigate the longitudinal associations of tobacco use in adolescence and SRB in adulthood. METHODS: Using a prospective design, we examined whether tobacco use in adolescence is associated with SRB (intentional self-injury, suicide ideation) in young adulthood in a population-based sample of 1330 twins (626 males, 704 females). The baseline and follow-up data were collected by professionally administered semi-structured poly-diagnostic interviews at ages 14 and 22, respectively. RESULTS: After adjusting for multiple potential confounders, those who reported early-onset of regular tobacco use had a significantly increased risk for intentional self-injury, such as cutting or burning, at age 22 (adjusted odds ratio [AOR] 4.57, 95% CI 1.93-10.8) in comparison to those who had not at all initiated tobacco use. Also, daily cigarette smoking at baseline was associated with future intentional self-injury (AOR 4.45, 95% CI 2.04-9.70). Early-onset tobacco use was associated with suicidal ideation in females (AOR 3.69, 95% CI 1.56-8.72) but not in males. Considering any SRB, baseline daily smokers (AOR 2.13, 95% CI 1.12-4.07) and females with early onset of regular tobacco use (AOR 3.97, 95% CI 1.73-9.13) had an increased likelihood. Within-family analyses among twin pairs discordant for exposure and outcome controlling for familial confounds showed similar, albeit statistically non-significant, associations. CONCLUSION: Early-onset tobacco use in adolescence is longitudinally associated with SRB (intentional self-injury and/or suicide ideation) in young adulthood, particularly among females. Further investigation may reveal whether this association has implications for prevention of SRB in adolescence and young adulthood.

18.
J Stud Alcohol Drugs ; 78(6): 817-826, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29087815

RESUMO

OBJECTIVE: Social relationships, such as committed partnerships, limit risky behaviors like heavy drinking, in part, because of increased social control. The current analyses examine whether involvement in committed relationships or social support extend beyond a main effect to limit genetic liability in heavy drinking (gene-environment interaction) during young adulthood. METHOD: Using data from the young adult wave of the Finnish Twin Study, FinnTwin12 (n = 3,269), we tested whether involvement in romantic partnerships or social support moderated genetic influences on heavy drinking using biometric twin modeling for gene-environment interaction. RESULTS: Involvement in a romantic partnership was associated with a decline in genetic variance in both males and females, although the overall magnitude of genetic influence was greater in males. Sex differences emerged for social support: increased social support was associated with increased genetic influence for females and reduced genetic influence for males. CONCLUSIONS: These findings demonstrate that social relationships are important moderators of genetic influences on young adult alcohol use. Mechanisms of social control that are important in limiting genetic liability during adolescence extend into young adulthood. In addition, although some relationships limit genetic liability equally, others, such as extensive social networks, may operate differently across sex.


Assuntos
Consumo de Bebidas Alcoólicas/epidemiologia , Interação Gene-Ambiente , Gêmeos , Adolescente , Adulto , Consumo de Bebidas Alcoólicas/genética , Criança , Feminino , Finlândia , Humanos , Masculino , Adulto Jovem
19.
Thorax ; 72(11): 1021-1027, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-29054888

RESUMO

BACKGROUND: We aimed to disentangle genetic and environmental causes in lung cancer while considering smoking status. METHODS: Four Nordic twin cohorts (43 512 monozygotic (MZ) and 71 895 same sex dizygotic (DZ) twin individuals) had smoking data before cancer diagnosis. We used time-to-event analyses accounting for censoring and competing risk of death to estimate incidence, concordance risk and heritability of liability to develop lung cancer by smoking status. RESULTS: During a median of 28.5 years of follow-up, we recorded 1508 incident lung cancers. Of the 30 MZ and 28 DZ pairs concordant for lung cancer, nearly all were current smokers at baseline and only one concordant pair was seen among never smokers. Among ever smokers, the case-wise concordance of lung cancer, that is the risk before a certain age conditional on lung cancer in the co-twin before that age, was significantly increased compared with the cumulative incidence for both MZ and DZ pairs. This ratio, the relative recurrence risk, significantly decreased by age for MZ but was constant for DZ pairs. Heritability of lung cancer was 0.41 (95% CI 0.26 to 0.56) for currently smoking and 0.37 (95% CI 0.25 to 0.49) for ever smoking pairs. Among smoking discordant pairs, the pairwise HR for lung cancer of the ever smoker twin compared to the never smoker co-twin was 5.4 (95% CI 2.1 to 14.0) in MZ pairs and 5.0 (95% CI 3.2 to 7.9) in DZ pairs. CONCLUSIONS: The contribution of familial effects appears to decrease by age. The discordant pair analysis confirms that smoking causes lung cancer.


Assuntos
Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/genética , Fumar/efeitos adversos , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Estudos de Coortes , Seguimentos , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
20.
Int J Public Health ; 62(7): 819-829, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28488098

RESUMO

OBJECTIVES: To investigate longitudinal associations of smoking and a change in smoking status with leisure-time physical inactivity. In addition, to control whether familial confounding (genetics and shared environment) influences the associations. METHODS: Data were based on the population-based Finnish Adult Twin Cohort of 5254 twin individuals born in 1945-1957 (41% men) and who participated in all four surveys over a 35-year follow-up (1975-2011). Logistic and conditional logistic regression models with multiple covariates were used for analyses. RESULTS: Compared to never-smokers, long-term daily smokers (1975-1990) had the highest likelihood for both long-term inactivity and to change into inactive by 2011. Recurrent smoking was associated with long-term inactivity. Instead, in comparison to persistent daily smokers, quitting smoking decreased the likelihood of becoming physically inactive at leisure time. The associations remained in the analyses which accounted for multiple covariates and/or familial confounding. CONCLUSIONS: Daily smoking increases the likelihood of remaining or becoming physically inactive over the decades. Our results emphasize not only the importance of preventing smoking initiation, but also to support early smoking cessation in promotion of lifelong physical activity.


Assuntos
Atividades de Lazer , Comportamento Sedentário , Fumar/psicologia , Gêmeos/psicologia , Adolescente , Adulto , Idoso , Feminino , Finlândia/epidemiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fumar/epidemiologia , Inquéritos e Questionários , Gêmeos/estatística & dados numéricos , Adulto Jovem
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