Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.

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BackgroundThis study investigates the relationship between parental drinking and school adjustment in a total population sample of adolescents, with independent reports from mothers, fathers, and adolescents. As a group, children of alcohol abusers have previously been found to exhibit lowered academic achievement. However, few studies address which parts of school adjustment that may be impaired. Both a genetic approach and social strains predict elevated problem scores in these children. Previous research has had limitations such as only recruiting cases from clinics, relying on single responders for all measures, or incomplete control for comorbid psychopathology. The specific effects of maternal and paternal alcohol use are also understudied.MethodsIn a Norwegian county, 88% of the population aged 13-19 years participated in a health survey (N = 8984). Among other variables, adolescents reported on four dimensions of school adjustment, while mothers and fathers reported their own drinking behaviour. Mental distress and other control variables were adjusted for. Multivariate analysis including generalized estimation equations was applied to investigate associations.ResultsCompared to children of light drinkers, children of alcohol abusers had moderately elevated attention and conduct problem scores. Maternal alcohol abuse was particularly predictive of such problems. Children of abstainers did significantly better than children of light drinkers. Controlling for adolescent mental distress reduced the association between maternal abuse and attention problems. The associations between parental reported drinking and school adjustment were further reduced when controlling for the children's report of seeing their parents drunk, which itself predicted school adjustment. Controlling for parental mental distress did not reduce the associations.ConclusionsParental alcohol abuse is an independent risk factor for attention and conduct problems at school. Some of the risk associated with mothers' drinking is likely to be mediated by adolescent mental distress. Despite lowered adjustment on the externalizing dimensions, children of alcohol abusers report that they enjoy being at school as much as other children.

The relationship between alcohol consumption and dementia risk is unclear. This investigation estimates the association between alcohol consumption reported in a population-based study in the mid-1980s and the risk for dementia up to 27 years later. The entire adult population in one Norwegian county was invited to the Nord-Trøndelag Health Study during 1984–1986 (HUNT1): 88 % participated. The sample used in this study includes HUNT1 participants born between 1905 and 1946 who completed the questionnaire assessing alcohol consumption. A total of 40,435 individuals, of whom 1084 have developed dementia, are included in the analysis adjusted for age, sex, years of education, hypertension, obesity, smoking, and symptoms of depression. When adjusting for age and sex, and compared to reporting consumption of alcohol 1–4 times during the last 14 days (drinking infrequently), both abstaining from alcohol and reporting consumption of alcohol five or more times (drinking frequently) were statistically significantly associated with increased dementia risk with hazard ratios of 1.30 (95 % CI 1.05–1.61) and 1.45 (1.11–1.90), respectively. In the fully adjusted analysis, drinking alcohol frequently was still significantly associated with increased dementia risk with a hazard ratio of 1.40 (1.07–1.84). However, the association between dementia and abstaining from alcohol was no longer significant (1.15, 0.92–1.43). Equivalent results for Alzheimer’s disease and vascular dementia indicated the same patterns of associations. When adjusting for other factors associated with dementia, frequent alcohol drinking, but not abstaining from alcohol, is associated with increased dementia risk compared to drinking alcohol infrequently.

Spouses tend to have similar lifestyles. We explored the degree to which spouse similarity in alcohol use, smoking, and physical exercise is caused by non-random mating or convergence. We used data collected for the Nord-Trøndelag Health Study from 1984 to 1986 and prospective registry information about when and with whom people entered marriage/cohabitation between 1970 and 2000. Our sample included 19,599 married/cohabitating couples and 1,551 future couples that were to marry/cohabitate in the 14-16 years following data collection. All couples were grouped according to the duration between data collection and entering into marriage/cohabitation. Age-adjusted polychoric spouse correlations were used as the dependent variables in non-linear segmented regression analysis; the independent variable was time. The results indicate that spouse concordance in lifestyle is due to both non-random mating and convergence. Non-random mating appeared to be strongest for smoking. Convergence in alcohol use and smoking was evident during the period prior to marriage/cohabitation, whereas convergence in exercise was evident throughout life. Reduced spouse similarity in smoking with relationship duration may reflect secular trends.