Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study

BACKGROUND: Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. METHODS: Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. RESULTS: Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. CONCLUSIONS: These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

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

Not by g alone: The benefits of a college education among individuals with low levels of general cognitive ability

In a longitudinal sample of 2593 individuals, we investigated the frequency individuals with IQs ≤ 90 completed college and whether these individuals experienced the same social and economic benefits higher-IQ college graduates did. Although the majority of individuals with IQs ≤ 90 did not have a college degree, approximately one in three women and one in five men did. The magnitude of the college effect on occupational status, income, financial independence and law abidingness was independent of IQ level, a finding replicated using the longitudinal NLSY97 sample. Additional analyses suggested the association of college with occupational status was causal and that the educational success of individuals with low average IQs may depend on personality factors, family socioeconomic status and genetic endowment. We discuss our finding in the context of the recent expansion in college attainment as well as the dearth of research on individuals with low average IQs

Not by g alone: The benefits of a college education among individuals with low levels of general cognitive ability

In a longitudinal sample of 2593 individuals, we investigated the extent to which individuals with IQs ≤ 90 completed college and when they did whether they experienced the same social and economic benefits of higher-IQ individuals who completed college. We found that while the majority of individuals with IQs ≤ 90 did not have a college degree, approximately one in three women and one in five men did. Importantly, the magnitude of the college effect on occupational status, income, financial independence and law abidingness was independent of IQ level, a finding we replicated using the longitudinal NLSY97 sample. Additional analysis suggested that the association of college with occupational status was causal and that the educational success of individuals with low average IQs may depend on personality factors, family socioeconomic status and genetic endowment. We discuss our finding in the context of the recent expansion in college attainment as well as the relative dearth of research on individuals with low average IQs

Parent contributions to the development of political attitudes in adoptive and non-adoptive families

Where do our political attitudes come from? Early research into the etiology of socially relevant beliefs attributed their origin primarily to the social world in which we develop. The observation that similar beliefs are reflected in our family and immediate social environments suggested that children learn these beliefs through the process of socialization. Genetically sensitive study designs later observed that the sociopolitical beliefs of identical twins are more similar than those of non-identical twins, despite being reared in the same environment, leading to an understanding of the role of genetics in the development of social attitudes. However, it has remained unclear whether and to what extent parents influence the development of these attitudes apart from or in addition to their genetic contribution. In a unique sample of 394 adoptive and biological families with adult offspring M age = 31.8, SD = 2.7), we demonstrate strong correlations between attitudes of parents with both adoptive and non-adoptive offspring. Biometric modeling reveals a significant contribution of both maternal and paternal phenotypes apart from and in addition to genetic contribution, including evidence for gene-environment correlation. These findings have significant implications for the origin and development of political and social attitudes in a modern political sphere where the etiology of such beliefs may be more important than ever to many

Parent contributions to the development of political attitudes in adoptive and non-adoptive families

Where do our political attitudes come from? Early research into the etiology of socially relevant beliefs attributed their origin primarily to the social world in which we develop. The observation that similar beliefs are reflected in our family and immediate social environments suggested that children learn these beliefs through the process of socialization. Genetically sensitive study designs later observed that the sociopolitical beliefs of identical twins are more similar than those of non-identical twins, despite being reared in the same environment, leading to an understanding of the role of genetics in the development of social attitudes. However, it has remained unclear whether and to what extent parents influence the development of these attitudes apart from or in addition to their genetic contribution. In a unique sample of 394 adoptive and biological families with adult offspring (M age = 31.8, SD = 2.7), we demonstrate strong correlations between attitudes of parents with both adoptive and non-adoptive offspring. Biometric modeling reveals a significant contribution of both maternal and paternal phenotypes apart from and in addition to genetic contribution, including evidence for gene-environment correlation. These findings have significant implications for the origin and development of political and social attitudes in a modern political sphere where the etiology of such beliefs may be more important than ever to many

Data

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Educational attainment, health outcomes and mortality: a within-sibship Mendelian randomization study

Background Previous Mendelian randomization (MR) studies using population samples (population MR) have provided evidence for beneficial effects of educational attainment on health outcomes in adulthood. However, estimates from these studies may have been susceptible to bias from population stratification, assortative mating and indirect genetic effects due to unadjusted parental genotypes. MR using genetic association estimates derived from within-sibship models (within-sibship MR) can avoid these potential biases because genetic differences between siblings are due to random segregation at meiosis. Methods Applying both population and within-sibship MR, we estimated the effects of genetic liability to educational attainment on body mass index (BMI), cigarette smoking, systolic blood pressure (SBP) and all-cause mortality. MR analyses used individual-level data on 72 932 siblings from UK Biobank and the Norwegian HUNT study, and summary-level data from a within-sibship Genome-wide Association Study including >140 000 individuals. Results Both population and within-sibship MR estimates provided evidence that educational attainment decreased BMI, cigarette smoking and SBP. Genetic variant-outcome associations attenuated in the within-sibship model, but genetic variant-educational attainment associations also attenuated to a similar extent. Thus, within-sibship and population MR estimates were largely consistent. The within-sibship MR estimate of education on mortality was imprecise but consistent with a putative effect. Conclusions These results provide evidence of beneficial individual-level effects of education (or liability to education) on adulthood health, independently of potential demographic and family-level confounders.Peer reviewe

Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects

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