Osteoporotic fractures in second-generation immigrants and Swedish natives.

In this national study of osteoporotic fractures in second-generation immigrants in Sweden, we found a similar risk of osteoporotic fractures in general compared to Swedish natives, which suggests that environmental factors are important for the high risk of osteoporotic fractures in Nordic countries. INTRODUCTION: Second generation immigrants may have a similar environment as individuals with two native-born parents. These individuals may be of interest to study concerning whether environmental or hereditary factors could be mostly associated to the risk of osteoporotic fractures. The aim of this study was to analyse the risk of osteoporotic fractures in second-generation immigrants compared to Swedish natives. METHODS: This was a nationwide study of individuals aged 50 years of age and older (N = 1,377,035; 691,750 men and 685,285 women). Osteoporotic fractures were defined as at least one registered diagnosis of fractures in the hip, humerus, forearm or vertebrae, in the National Patient Register between January 1, 1998, and December 31, 2012. Cox regression analysis was used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of incident osteoporotic fractures in second generation immigrants compared to Swedish natives. The Cox regression models were adjusted for age, comorbidities and for sociodemographic status. RESULTS: A total of 114,505 osteoporotic fractures were registered, 109,622 (8.4%) were among individuals with Swedish-born parents and 4883 (7.5%) among those with foreign-born parents, with distal forearm fractures dominating in general (44.9%). Fully adjusted HRs (95% CI) were for all immigrants 0.95 (95% CI, 0.91-0.99), for men 0.96 (95% CI, 0.89-1.04) and for women 0.95 (95% CI, 0.90-1.00). CONCLUSIONS: We observed a similar risk of osteoporotic fractures among second-generation immigrants as in Swedish natives, which suggests that environmental factors are important for osteoporotic fractures.

Osteoporotic fractures among foreign-born individuals: a national Swedish study.

In this national study of osteoporotic fractures in foreign-born individuals, we found a lower risk of osteoporotic fractures in general among foreign-born individuals compared with Swedish-born, especially in immigrants from southern Europe. A higher risk was found among some groups, i.e. men and women from Bosnia and Iraq and men from Lebanon. INTRODUCTION: The aim of this study was to analyse risk of osteoporotic fractures in foreign-born individuals compared with Swedish-born individuals. METHODS: This was a nationwide study of individuals 50 years of age and older (N = 2,775,736). Osteoporotic fractures were defined as at least one registered diagnosis of fractures in the hip, humerus, forearm or vertebrae, in the National Patient Register between January 1, 1998, and December 31, 2012. Cox regression analysis was used to estimate the relative risk (hazard ratios (HR) with 99% confidence intervals (CI)) of incident osteoporotic fractures in foreign-born compared with Swedish-born individuals. The Cox regression models were stratified by sex and adjusted for age, comorbidities and sociodemographic status. RESULTS: A total of 362,899 osteoporotic fractures were registered (96,847 among men and 266,052 among women), with hip fractures dominating (54.0% among men, 42.6% among women). Fully adjusted HRs (99% CI) were for all immigrant men 0.75 (99% CI, 0.73-0.78) and women 0.83 (99% CI, 0.81-0.84), with significantly lower HRs among most groups but with higher HRs in certain countries. For the specific fractures, higher HRs were found for lower forearm fractures for men from Asia and for vertebral fractures among women from Asia. CONCLUSIONS: We observed a generally lower risk of osteoporotic fractures among first-generation immigrants, with few exceptions.

Influence of family history on risk of second primary cancers and survival in patients with squamous cell skin cancer.

BACKGROUND: Patients with squamous cell skin cancer (SCC) have an excellent prognosis but second primary cancers (SPCs) weaken survival prospects. Family history is a known risk factor for cancer but whether it is a risk factor for SPC in patients with SCC is not known. OBJECTIVES: To quantify the risk of family history on SPCs in patients with SCC and estimate survival probabilities of patients with SPCs depending on family history. METHODS: With 13 945 histologically verified SCCs, relative risks (RRs) were estimated for family history using a generalized regression model. For survival analysis, hazard ratios (HRs) were assessed using a multivariable Cox proportional-hazards model. RESULTS: Family history of invasive SCC increased risk of second invasive SCC [RR = 42·92, 95% confidence interval (CI) 33·69-50·32] compared with risk without family history (RR 19·12, 95% CI 17·88-21·08). Family history of any nonskin cancer in invasive SCC increased risk of the same cancers to be diagnosed as SPC (RRFH = 1·48, 95% CI 1·35-1·61 vs. RRno FH = 1·40, 95% CI 1·32-1·48); significant increases were observed for seven different nonskin cancers. Most results were replicated for in situ SCC. SPC was deleterious for survival irrespective of family history; HR for patients with SPC was 4·28 (95% CI 3·83-4·72) vs. those without SPC (1·04). CONCLUSIONS: Family history of nonskin cancer was associated with approximately a doubling of risk for SPCs in patients with SCC. SPC increases the death rate in patients with SCC 3-4 times, irrespective of family history. Taking family history into account at SCC diagnosis may help prevention or early detection of SPCs. What's already known about this topic? Second primary cancers (SPCs) are frequently diagnosed in patients with invasive and in situ squamous cell carcinoma (SCC); some epidemiological studies suggest a link to immune dysfunction. Family history of cancer is a risk factor for practically all first primary cancers but whether it also influences risk of SPCs in patients with SCC is not known. The possible influence of family history on survival in patients with SCC remains to be established. Linked Comment: Youlden and Baade. Br J Dermatol 2020; 183:414-415.

Epilepsy in second-generation immigrants: a cohort study of all children up to 18 years of age in Sweden.

BACKGROUND AND PURPOSE: Our purpose was to study the association between country of birth and incident epilepsy in second-generation immigrants in Sweden. METHODS: The study population included all children (n = 4 023 149) aged up to 18 years in Sweden. Epilepsy was defined as at least one registered diagnosis of epilepsy in the National Patient Register. The incidence of epilepsy, using individuals with Swedish-born parents as referents, was assessed by Cox regression, expressed in hazard ratios (HRs) and 95% confidence interval (95% CI). All models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, neighbourhood socioeconomic status and comorbid conditions, also using data from the Total Population Register. RESULTS: A total of 26 310 individuals had a registered epilepsy event, i.e. 6.5/1000 (6.6/1000 amongst boys and 6.3/1000 amongst girls). After adjustment, the risk of epilepsy was lower than in children of Swedish-born parents. Amongst girls the significant HR was 0.85 (95% CI 0.81-0.88), but in boys only when adjusting also for comorbidity (HR 0.96, 95% CI 0.92-0.99). Amongst specific immigrant groups, a higher incidence of epilepsy was observed amongst boys with parents from Turkey and Africa, but not when adjusting for comorbidity, and a lower risk was observed in many other groups (boys with parents from Latvia, girls with parents from Finland, Iceland, Southern Europe, countries from the former Yugoslavia, and Asia). CONCLUSION: The risk of epilepsy was lower in second-generation immigrant children compared to children with Swedish-born parents, but with substantial differences between different immigrant groups.

Different Characteristics and Heritabilities of Alcohol Use Disorder Classes: A Population-Based Swedish Study.

AIMS: The aims of the present study are to identify alcohol use disorder (AUD) classes among a population-based Swedish sample, determine if these classes differ by variables known to be associated with AUD and determine whether some AUD classes have stronger genetic influences than others. METHODS: A latent class analysis (LCA), based on types of registrations, was conducted on Swedish individuals with an AUD registration born between 1960 and 1990 (N = 184,770). These classes were then validated using demographics; patterns of comorbidity with drug abuse, psychiatric disorders and criminal behavior; and neighborhood-level factors, i.e. peer AUD and neighborhood deprivation. The degree of genetic and environmental influence was also investigated. RESULTS: The best-fit LCA had four classes: (a) outpatient/prescription, characterized by a mix of outpatient medical and prescription registrations, (b) low-frequency inpatient, characterized entirely by inpatient medical registrations, with the majority of individuals having one AUD registration, (c) high-frequency mixed, characterized by a mix of all four registration types, with the majority having four or more registrations and (d) crime, characterized almost entirely by criminal registrations. The highest heritability for both males and females was found for Class 3 (61% and 65%, respectively) and the lowest for Class 1 (20% for both), with shared environmental influences accounting for 10% or less of the variance in all Classes. CONCLUSIONS: Using comprehensive, nationwide registry data, we showed evidence for four distinct, meaningful classes of AUD with varying degrees of heritability.

Geographic proximity is associated with transmission of suicidal behaviour among siblings.

OBJECTIVE: The aim of this study was to clarify the role of 'contagion', or social transmission, in risk of suicidal behaviour (SB) among siblings. METHODS: We followed Swedish sibling pairs until one of them (S1; N = 111,848) was registered for a suicide attempt or completion. We tested the effect of geographic proximity between siblings on risk of a first SB registration of S1's sibling (S2). To control for familial confounding, we conducted complementary analyses of sibling trios (N = 701), comparing risk in different siblings as a function of their respective proximity to S1. RESULTS: The best-fitting model across sibling pairs included an effect of distance between siblings (HR = 0.96, 95% CI = 0.93-0.99). Hazard ratios declined quickly up to 25 km and largely stabilized beyond 150 km. Across all pairs, a larger age difference between siblings was associated with reduced SB risk (HR = 0.96 95% CI = 0.93-0.98). Findings were consistent within the sibling trios. CONCLUSIONS: Consistent with the concept of suicide contagion, risk of suicidal behaviour subsequent to a sibling's suicide completion or attempt is higher as a function of sibling closeness. These findings are robust to potentially confounding familial factors.

Aerobic fitness in late adolescence and the risk of cancer and cancer-associated mortality in adulthood: A prospective nationwide study of 1.2 million Swedish men.

BACKGROUND: The incidence of cancer has steadily risen. It is important to identify modifiable predictors in early life that may decrease cancer risks and mortality. The present study aims to investigate the relationship between aerobic fitness in adolescence and the subsequent risk of cancer and cancer-associated mortality. METHODS: The study included 1 185 439 Swedish men born between 1950 and 1980 that participated in the military conscription (mean age = 18 years). The results from the aerobic fitness test (Wmax) was linked to the risk of cancer and cancer-associated mortality during a 40-years' follow-up using Cox proportional hazards models. A co-sibling design was employed to take familial factors into account. RESULTS: During a mean follow-up of 27 years 15 093 cases of cancer and 4900 cancer-associated mortalities were registered. Higher Wmax (per additional 1 SD) was associated with a decreased risk of cancer at 40 years of follow-up (HR 0.93; 95% CI 0.91-0.96 for cancer and HR 0.82 95% CI 0.76-0.87 for cancer-associated mortality) but not at 5 years of follow-up (HR 1.03; 95% CI 0.99-1.07; and HR 1.04; 95% CI 0.97-1.12). In the co-sibling model the protective effects of high Wmax were increased at 40 years of follow-up for cancer (HR 0.91; 95% CI 0.85-0.98) and cancer-associated mortality (HR 0.78; 95% CI 0.68-0.89). CONCLUSIONS: These findings identify in late adolescence a potentially modifiable predictor of cancer, with higher aerobic fitness associated with a decreased risk of cancer incidence and mortality later in life.

The role of parent and offspring sex on risk for externalizing psychopathology in offspring with parental alcohol use disorder: a national Swedish study.

PURPOSE: The substantial literature showing that offspring of parents with alcohol use disorder (AUD) is at increased risk for externalizing psychopathology rarely examines the differential effects of parental and offspring sex. This literature also has other important limitations, such as modest sample sizes and use of unrepresentative samples. Using a large, nationwide Swedish sample, we aim to investigate the roles of parental and offspring sex in externalizing psychopathology among offspring with parental AUD. METHODS: AUD diagnosis and externalizing measures were obtained from national registries. Associations between outcomes and parental AUD were examined using logistic regressions. Parental and offspring sex effects were examined with interaction terms. RESULTS: Risks for externalizing disorders were increased in sons and daughters with parental AUD, with significant differences between sons and daughters for criminal behavior; maternal AUD had a greater impact than paternal AUD (regardless of offspring sex), but having two parents with AUD increased risk for all outcomes substantially more than having one parent; and maternal AUD increased risk of drug abuse for daughters more than sons, while paternal AUD increased risk of AUD and criminal behavior for sons more than daughters. CONCLUSIONS: Offspring of parents with AUD are at increased risk for externalizing psychopathology. Maternal and paternal AUD differentially affected sons' vs. daughters' risks for AUD, drug abuse, and criminal behavior. The transmission of psychopathology within the externalizing spectrum appears to have sex-specific elements.

The joint impact of cognitive performance in adolescence and familial cognitive aptitude on risk for major psychiatric disorders: a delineation of four potential pathways to illness.

How do joint measures of premorbid cognitive ability and familial cognitive aptitude (FCA) reflect risk for a diversity of psychiatric and substance use disorders? To address this question, we examined, using Cox models, the predictive effects of school achievement (SA) measured at age 16 and FCA-assessed from SA in siblings and cousins, and educational attainment in parents-on risk for 12 major psychiatric syndromes in 1 140 608 Swedes born 1972-1990. Four developmental patterns emerged. In the first, risk was predicted jointly by low levels of SA and high levels of FCA-that is a level of SA lower than would be predicted from the FCA. This pattern was strongest in autism spectrum disorders and schizophrenia, and weakest in bipolar illness. In these disorders, a pathologic process seems to have caused cognitive functioning to fall substantially short of familial potential. In the second pattern, seen in the internalizing conditions of major depression and anxiety disorders, risk was associated with low SA but was unrelated to FCA. Externalizing disorders-drug abuse and alcohol use disorders-demonstrated the third pattern, in which risk was predicted jointly by low SA and low FCA. The fourth pattern, seen in eating disorders, was directly opposite of that observed in externalizing disorders with risk associated with high SA and high FCA. When measured together, adolescent cognitive ability and FCA identified four developmental patterns leading to diverse psychiatric disorders. The value of cognitive assessments in psychiatric research can be substantially increased by also evaluating familial cognitive potential.

Transmission of alcohol use disorder across three generations: a Swedish National Study.

BACKGROUND: While risk for alcohol use disorder (AUD) is correlated in twins, siblings and parent-offspring pairs, we know little of how this syndrome is transmitted across three generations. METHOD: We examined 685 172 individuals born in Sweden from 1980 to 1990 with four grandparents, and both parents alive in 1980. AUD was assessed in all these individuals from nationwide medical, criminal and pharmacy registries. RESULTS: AUD was stably transmitted across three generations. Parent-child and grandparent-grandchild tetrachoric correlations equaled +0.25 and +0.12, respectively. Grandchild AUD risk did not vary as a function of the sex of the parent or grandparent. However, from grandparents and parents, transmission to grandchildren was stronger in same-sex than opposite-sex pairs. Compared with a grandchild with unaffected parents and grandparents, risk for AUD with a grandparent but no parent affected, a parent but no grandparent affected or both affected increased approximately 70% and 3 and 4-fold, respectively. Grandchildren with ⩾2 grandparents affected had a 40% greater AUD risk than those with only one affected. Tetrachoric correlations for AUD between offspring and great-aunts/uncles, and aunts/uncles equaled +0.06 and +0.13, respectively. CONCLUSIONS: The transmission of AUD in Sweden across three generations is relatively stable. An orderly pattern of resemblance is seen with correlations declining by approximately 50% between first and second, and second and third-degree relatives. While the transmission of risk from affected male and female relatives does not differ, we find consistent evidence for greater resemblance in same-sex v. opposite-sex across generational pairs of relatives.

Prediction of drug abuse recurrence: a Swedish National Study.

BACKGROUND: Relapse from drug abuse (DA) is common, but has rarely been studied in general population samples using a wide range of objective predictors. METHOD: Using nationwide registries, we ascertained 44 523 subjects first registered for DA between the ages of 15 and 40 in 1998 to 2004 and followed for 8 years. We predicted relapse in subjects defined as a second DA registration. We also predicted DA relapse in relative pairs concordant for DA but discordant for relapse. RESULTS: In multivariate regression analyses, the strongest predictors for relapse were prior criminal behavior, male sex, being on social welfare, low school achievement, prior alcoholism, and a high-risk father. A risk index trained from these analyses on random split-halves demonstrated a risk ratio of 1.11 [95% confidence intervals (CIs) 1.10-1.11] per decile and an ROC value of 0.70 (0.69-0.71). Co-relative analyses indicated that a modest proportion of this association was causal, with the remainder arising from familial confounders. A developmental structural equation model revealed a complex interviewing of risk pathways to DA with three key mediational hubs: low educational attainment, early age at first registration, and being on social welfare. CONCLUSIONS: In a general population sample, using objective registry information, DA relapse is substantially predictable. However, the identified risk factors may not be valid targets for interventions because many index familial risk and may not impact causally on probability of relapse. Risk for DA relapse may reflect an inter-weaving, over developmental time, of genetic-temperamental vulnerability, indices of externalizing behaviors and social factors reflecting deprivation.

The effect of mindfulness group therapy on a broad range of psychiatric symptoms: A randomised controlled trial in primary health care.

BACKGROUND: The need for psychotherapy in primary health care is on the increase but individual-based treatment is costly. The main aim of this randomised controlled trial (RCT) was to compare the effect of mindfulness-based group therapy (MGT) with treatment as usual (TAU), mainly individual-based cognitive behavioural therapy (CBT), on a broad range of psychiatric symptoms in primary care patients diagnosed with depressive, anxiety and/or stress and adjustment disorders. An additional aim was to compare the effect of MGT with TAU on mindful attention awareness. METHODS: This 8-week RCT took place in 2012 at 16 primary care centres in southern Sweden. The study population included both men and women, aged 20-64years (n=215). A broad range of psychiatric symptoms were evaluated at baseline and at the 8-week follow-up using the Symptom Checklist-90 (SCL-90). Mindful attention awareness was also evaluated using the Mindful Attention Awareness Scale (MAAS). RESULTS: In both groups, the scores decreased significantly for all subscales and indexes in SCL-90, while the MAAS scores increased significantly. There were no significant differences in the change in psychiatric symptoms between the two groups. The mindfulness group had a somewhat larger change in scores than the control group on the MAAS (P=0.06, non-significant). CONCLUSIONS: No significant differences between MGT and TAU, mainly individual-based CBT, were found in treatment effect. Both types of therapies could be used in primary care patients with depressive, anxiety and/or stress and adjustment disorders, where MGT has a potential to save limited resources. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01476371.

Risk of ocular manifestations in patients with giant cell arteritis: a nationwide study in Sweden.

OBJECTIVE: No large-scale nationwide study has determined the risk of ocular manifestations in patients with giant cell arteritis (GCA). The aim was to study the incidence and risk factors of ocular manifestations in patients with GCA in Sweden. METHOD: A national cohort was created by linking Swedish nationwide registers. GCA patients were identified from the Swedish Hospital Inpatient and Outpatient Registers between 2002 and 2010, and were followed until the development of ocular manifestations. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated for ocular manifestations in patients with GCA compared to those without GCA. RESULTS: We identified 3737 males and 8311 females with GCA. A total of 1618 individuals had subsequent ocular manifestations, representing 13.4% of the GCA patients. The overall SIR of ocular manifestations was 6.96 (95% CI 6.63-7.31). The risk for disorders of the optic nerve or visual tract was particularly high (SIR = 51.68, 95% CI 46.12-57.73). Men with GCA had a higher risk than women, and GCA patients without polymyalgia rheumatica (PMR) symptoms had a higher risk than those with PMR symptoms. Living outside big cities was negatively associated with ocular manifestations in GCA patients, whereas hypertension and diabetes were associated with an increased risk of ocular manifestations. CONCLUSION: The overall risk of ocular manifestations was higher in GCA patients than in the general population, especially for men and for those without PMR symptoms.

Familial associations of lymphoma and myeloma with autoimmune diseases.

Many B-cell neoplasms are associated with autoimmune diseases (AIDs) but most evidence is based on a personal rather than a family history of AIDs. Here we calculated risks for non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL) and multiple myeloma (MM) when family members were diagnosed with any of 44 different AIDs, or, independently, risk for AIDs when family members were diagnosed with a neoplasm. A total of 64 418 neoplasms and 531 155 AIDs were identified from Swedish nationwide health care records. NHL was associated with a family history of five AIDs, all increasing the risk, HL was associated with one AID increasing and three AIDs decreasing the risk while MM had no association. A family history of NHL was associated with eight, HL with seven and MM with seven different AIDs, nine increasing and 13 decreasing the risk. The present family data on B-cell neoplasms and AIDs show an approximately equal number of associations for risk increase and risk decrease, suggesting that inherited genes or gene-environment interactions may increase the risk or be protective. These results differed from published data on personal history of AID, which only report increased risks, often vastly higher and for different AIDs compared with the present data.

The role of marriage in criminal recidivism: a longitudinal and co-relative analysis.

AIMS: Marriage is associated with a reduced rate of criminal recidivism, but the underlying mechanisms have only partly been elucidated. We seek to clarify the nature of the association between marriage and recidivism and how that relationship may be moderated as a function of gender, deviance of spouse, a history of violence and familial risk. METHOD: We utilise a longitudinal cohort design consisting of Swedish men (n = 239 328) and women (n = 72 280), born between 1958 and 1986, who were convicted of at least one crime before age 20 and were not married prior to age 20. The analyses used Cox regression with marriage as a time-dependent covariate. We also perform co-relative analyses in sibling and first cousin pairs. RESULTS: Marriage after a first crime substantially reduces risk of recidivism in both males (hazard ratio (HR) with key covariates and 95% confidence intervals 0.55, 0.53-0.57) and females (HR = 0.38, 0.34-0.42), although the effect is stronger in females. Marriage to a deviant spouse increases recidivism rates in males. In males, a history of violent criminality and high familial risk, respectively, decrease and increase sensitivity to the protective effect of marriage on recidivism. Consistent with a causal effect of marriage on recidivism, marriage was associated with a decline in risk for criminal relapse comparable with that in the population in both male-male sibling pairs (raw HR = 0.53, 0.45-0.62) and cousin pairs (HR = 0.55, 0.47, 0.65) concordant for prior convictions. CONCLUSIONS: The protective effect of marriage on risk for criminal recidivism is likely largely causal and is of importance in both males and females. Those at high familial risk for criminal behaviour are more sensitive to the protective effects of marriage.

Interactive effects of obesity and physical fitness on risk of ischemic heart disease.

BACKGROUND/OBJECTIVES: Obesity and low physical fitness are known risk factors for ischemic heart disease (IHD), but their interactive effects are unclear. Elucidation of interactions between these common, modifiable risk factors may help inform more effective preventive strategies. We examined interactive effects of obesity, aerobic fitness and muscular strength in late adolescence on risk of IHD in adulthood in a large national cohort. SUBJECTS/METHODS: We conducted a national cohort study of all 1 547 407 military conscripts in Sweden during 1969-1997 (97-98% of all 18-year-old males each year). Aerobic fitness, muscular strength and body mass index (BMI) measurements were examined in relation to IHD identified from outpatient and inpatient diagnoses through 2012 (maximum age 62 years). RESULTS: There were 38 142 men diagnosed with IHD in 39.7 million person years of follow-up. High BMI or low aerobic fitness (but not muscular strength) was associated with higher risk of IHD, adjusting for family history and socioeconomic factors. The combination of high BMI (overweight/obese vs normal) and low aerobic fitness (lowest vs highest tertile) was associated with highest IHD risk (incidence rate ratio, 3.11; 95% confidence interval (CI), 2.91-3.31; P<0.001). These exposures had no additive and a negative multiplicative interaction (that is, their combined effect was less than the product of their separate effects). Low aerobic fitness was a strong risk factor even among those with normal BMI. CONCLUSIONS: In this large cohort study, low aerobic fitness or high BMI at age 18 was associated with higher risk of IHD in adulthood, with a negative multiplicative interaction. Low aerobic fitness appeared to account for a similar number of IHD cases among those with normal vs high BMI (that is, no additive interaction). These findings suggest that interventions to prevent IHD should begin early in life and include not only weight control but aerobic fitness, even among persons of normal weight.

Social and economic consequences of alcohol use disorder: a longitudinal cohort and co-relative analysis.

BACKGROUND: Although alcohol use disorder (AUD) is associated with future risk for psychosocial dysfunction, the degree to which this arises from a direct causal effect of AUD on functioning v. from correlated risk factors (also known as confounders) is less clearly established. METHOD: AUD was assessed from Swedish medical, criminal and pharmacy registries. In a large general population cohort, using Cox proportional hazard and regression models, we predicted from the onset of AUD four outcomes: early retirement, unemployment, social assistance, and individual income. We then examined the degree to which these associations were attenuated by relevant confounders as well as by the use of discordant cousin, half-sibling, full-sibling, and monozygotic twin pairs. RESULTS: In males, AUD most strongly predicted social assistance [hazard ratio (HR) 8.27, 95% confidence interval (CI) 7.96-8.59], followed by early retirement (HR 5.63, 95% CI 5.53-5.72) and unemployment (HR 2.75, 95% CI 2.65-2.85). For income at age 50, AUD was associated with a decrease in income of 0.24 s.d.s (95% CI -0.25 to -0.23). Results were similar in females. Modest to moderate attenuation of these associations was seen in both sexes after the addition of relevant covariates. These associations were reduced but remained robust in discordant co-relative pairs, including monozygotic twins. CONCLUSIONS: Our results suggest that AUD has a causal impact on a range of measures reflective of psychosocial dysfunction. These findings provide strong support for the drift hypothesis. However, some of the associations between AUD and dysfunction appear to be non-causal and result from shared risk factors, many of which are likely familial.

A developmental model for alcohol use disorders in Swedish men.

BACKGROUND: Alcohol use disorder (AUD) is a classic multifactorial syndrome and it is critical to understand the diversity of the relevant risk factors and how they inter-relate over development. METHOD: We examined 21 risk factors for AUD in four developmental tiers reflecting (i) birth, (ii) childhood and early adolescence, (iii) late adolescence, and (iv) early adulthood in 47 414 Swedish men of whom 3907 (8.2%) were registered for AUD at or after age 25 with a mean length of follow-up of 33.9 (6.6) years. Structural equational model fitting was performed using Mplus. RESULTS: The best-fitting model provided a good fit to the data and explained 23.4% of the variance in AUD. The five strongest predictors were: externalizing behaviors, criminal behavior, father's alcohol consumption, genetic risk, and low educational attainment. Two developmentally early familial/genetic risk factors had substantial direct paths to AUD: father's alcohol consumption and genetic liability. Other broad developmental pathways to risk for AUD were evident: externalizing, psychosocial and internalizing. Overall, the externalizing pathway to AUD was the strongest. However, these pathways were substantially interwoven over time such that risk factors from one domain were commonly predicted by and/or predicted risk factors from the other broad domains of risk. CONCLUSION: AUD in men is an etiologically complex syndrome influenced by familial-genetic, psychosocial, internalizing, and especially externalizing risk factors that act and interact over development and have complicated mediational pathways.