Socio-economic differences in body mass index: the contribution of genetic factors.

BACKGROUND: Higher mean body mass index (BMI) among lower socioeconomic position (SEP) groups is well established in Western societies, but the influence of genetic factors on these differences is not well characterized. METHODS: We analyzed these associations using Finnish health surveys conducted between 1992 and 2017 (N = 33 523; 53% women) with information on measured weight and height, polygenic risk scores of BMI (PGS-BMI) and linked data from administrative registers to measure educational attainment, occupation-based social class and personal income. RESULTS: In linear regressions, largest adjusted BMI differences were found between basic and tertiary educated men (1.4 kg/m2, 95% confidence interval [CI] 1.2; 1.6) and women (2.5 kg/m2, 95% CI 2.3; 2.8), and inverse BMI gradients were also found for social class and income. These SEP differences arose partly because mean PGS-BMI was higher and partly because PGS-BMI predicted BMI more strongly in lower SEP groups. The inverse SEP gradients of BMI were steeper in women than in men, but sex differences were not found in the genetic contributions to these differences. CONCLUSIONS: Better understanding of the interplay between genes and environment provides insight into the mechanisms explaining SEP differences in BMI.

Polygenic Prediction of Education and Its Role in the Intergenerational Transmission of Education: Cohort Changes Among Finnish Men and Women Born in 1925-1989.

Major changes in the educational distribution of the population and in institutions over the past century have affected the societal barriers to educational attainment. These changes can possibly result in stronger genetic associations. Using genetically informed, population-representative Finnish surveys linked to administrative registers, we investigated the polygenic associations and intergenerational transmission of education for those born between 1925 and 1989. First, we found that a polygenic index (PGI) designed to capture genetic predisposition to education strongly increased the predictiveness of educational attainment in pre-1950s cohorts, particularly among women. When decomposing the total contribution of PGI across different educational transitions, the transition between the basic and academic secondary tracks was the most important. This transition accounted for 60-80% of the total PGI-education association among most cohorts. The transition between academic secondary and higher tertiary levels increased its contribution across cohorts. Second, for cohorts born between 1955 and 1984, we observed that one eighth of the association between parental and one's own education is explained by the PGI. There was also an increase in the intergenerational correlation of education among these cohorts, which was partly explained by an increasing association between family education of origin and the PGI.

Marital status and genetic liability independently predict coronary heart disease incidence.

AIMS: Married individuals have a lower coronary heart disease (CHD) risk than non-married, but the mechanisms behind this are not fully understood. We analyzed whether genetic liability to CHD may affect these associations. METHODS: Marital status, a polygenic score of CHD (PGS-CHD), and other risk factors for CHD were measured from 35,444 participants (53% female) in Finnish population-based surveys conducted between 1992 and 2012. During the register-based follow-up until 2020, there were 2439 fatal and non-fatal incident CHD cases. The data were analyzed using linear and Cox regression models. RESULTS: Divorced and cohabiting men and women had a higher genetic risk of CHD than married individuals, but the difference was very small (0.023-0.058 standard deviation of PGS-CHD, p-values 0.011-0.429). Both marital status and PGS-CHD were associated with CHD incidence, but the associations were largely independent. Adjusting for behavioral and metabolic risk factors for CHD explained part of these associations (11-20%). No interaction was found between marital status and PGS-CHD for CHD incidence. CONCLUSIONS: We showed minor differences between the marital status categories in PGS-CHD and demonstrated that marital status and genetic liability predicted CHD incidence largely independently. This emphasizes the need to measure multiple risk factors when predicting CHD risk.

Genetic propensity to depression and the role of partnership status.

Social relationships and genetic propensity are known to affect depression risk, but their joint effects are poorly understood. This study examined the association of a polygenic index for depression with time to antidepressant (AD) purchasing and the moderating role of partnership status. We analysed data from 30,192 Finnish individuals who participated in the FINRISK and Health 2000 and 2011 surveys and had register and medication data available. We measured genetic risk with a polygenic index (PGI) for depression. Depression was assessed through antidepressant purchases. We estimated an accelerated failure time model with partnership status as time-varying and different sets of confounder adjustments. The predicted cumulative hazard of antidepressant purchasing varied across PGI and partnership status. At follow-up year 10, being widowed was associated with the largest cumulative hazard of 0.34 (95%CI: 0.28-0.39) in the 80th and 0.20 (95%CI: 0.17-0.23) in the 20th PGI percentile, followed by divorced, single, married and cohabiting. Cohabiting was associated with a cumulative hazard of 0.19 (95%CI: 0.16-0.23) in the 80th and 0.11 (95%CI: 0.1-0.13) in the 20th PGI percentile. We found no evidence for an interaction between the PGI and partnership status. Results were robust to different model specifications, gender stratification, and the choice of PGI. Although antidepressant purchasing correlated with both PGI and partnership status, we found no evidence that partnership status could partially offset or amplify the association between the PGI for depression and antidepressant purchasing incidence.

Association between genetic risk of alcohol consumption and alcohol-related morbidity and mortality under different alcohol policy conditions: Evidence from the Finnish alcohol price reduction of 2004.

AIMS: Harmful alcohol consumption is influenced by both genetic susceptibility and the price of alcohol. Many previous studies have observed that genetic susceptibility to consumption of alcohol is more predictive in less restrictive drinking conditions. We assess whether such a pattern applies when the prices of alcoholic beverages are decreased. DESIGN: Data consist of genetically informed population-representative surveys (FINRISK 1992, 1997, 2002 and Health 2000) linked to administrative registers. We analysed the interaction between a polygenic score (PGS) for alcoholic drinks per week consumed and price reduction in predicting the incidence of alcohol-related hospitalizations and deaths in difference-in-difference and interrupted time-series frameworks. SETTING: Individuals in Finland were followed quarter-yearly from 1 March 2000 to 31 May 2008. PARTICIPANTS: A total of 22 152 individuals (607 132-person quarter-years, 1399 outcome events) aged 30-79 years. INTERVENTION: A natural experiment stemming from the alcohol tax reduction in March 2004 and import deregulation in May 2004. MEASUREMENTS: Outcome was quarter-yearly-measured alcohol-related death or hospitalization. The independent variables of main interest were PGS and a price reform indicator. We adjusted for gender, age, age squared, season, 10 first principal components of the genome, data collection round and genotyping batch. FINDINGS: Both alcohol price reduction and one standard deviation change in PGS were associated with alcohol-related health outcomes; odds ratios (ORs) were 1.32, 95% confidence interval (CI) = 1.13, 1.53 and 1.26, 95% CI = 1.12, 1.42 in the 8-year follow-up, respectively. The association between PGS and alcohol-related morbidity was similar before and after the alcohol price reform (PGS × price reform interaction OR = 0.96, 95% CI = 0.81, 1.14). These results were robust across different follow-up periods and measurement and analysis strategies. CONCLUSIONS: Although the decrease of alcohol price in Finland in 2004 substantially increased overall alcohol-related morbidity and mortality, the genetic susceptibility to alcohol consumption did not become more manifest in predicting them.

Height, social position and coronary heart disease incidence: the contribution of genetic and environmental factors.

BACKGROUND: The associations between height, socioeconomic position (SEP) and coronary heart disease (CHD) incidence are well established, but the contribution of genetic factors to these associations is still poorly understood. We used a polygenic score (PGS) for height to shed light on these associations. METHODS: Finnish population-based health surveys in 1992-2011 (response rates 65-93%) were linked to population registers providing information on SEP and CHD incidence up to 2019. The participants (N=29 996; 54% women) were aged 25-75 at baseline, and there were 1767 CHD incident cases (32% in women) during 472 973 person years of follow-up. PGS-height was calculated based on 33 938 single-nucleotide polymorphisms, and residual height was defined as the residual of height after adjusting for PGS-height in a linear regression model. HRs of CHD incidence were calculated using Cox regression. RESULTS: PGS-height and residual height showed clear gradients for education, social class and income, with a larger association for residual height. Residual height also showed larger associations with CHD incidence (HRs per 1 SD 0.94 in men and 0.87 in women) than PGS-height (HRs per 1 SD 0.99 and 0.97, respectively). Only a small proportion of the associations between SEP and CHD incidence was statistically explained by the height indicators (6% or less). CONCLUSIONS: Residual height associations with SEP and CHD incidence were larger than for PGS-height. This supports the role of material and social living conditions in childhood as contributing factors to the association of height with both SEP and CHD risk.

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.

Changes in sibling similarity in education among Finnish cohorts born in 1950-89: the contribution of paternal and maternal education.

Among the many social characteristics that run in the family, education is one of the most strongly persistent. The long-term changes in educational reproduction within families and across generations and the gender-specific drivers of these changes remain partially unclear. Using population data for all Finnish siblings and their parents, we assessed the level of and trends in the intergenerational persistence of education among cohorts born between 1950 and 1989. The variance in education shared among siblings was 37% and remained stable over time. Parental education steadily increased its explanatory power in the shared variance, from 30% among cohorts born in the 1950s to 40% among cohorts born in the 1970s and 1980s. The direct contribution of maternal education net of paternal education for sibling similarity more than doubled across cohorts (from 5% in 1950 to 13% in 1989). The direct contribution of paternal education (10-12%) remained stable. Same-gender siblings resembled each other in education more closely than their opposite-gender counterparts. The growing importance of maternal education over time, which surpasses the predictive power of paternal education, demonstrates an important qualitative change in the determinants of educational stratification. The growing importance of mothers' education can plausibly result from the strengthening meritocratic achievement of women in education and the associated increase of women in defining the social position of the family. Incorporating the education of both parents in future analyses of intergenerational reproduction of education will probably be increasingly salient.

Joint associations of depression, genetic susceptibility and the area of residence for coronary heart disease incidence.

BACKGROUND: Depression is a risk factor for coronary heart disease (CHD), but less is known whether genetic susceptibility to CHD or regional-level social indicators modify this association. METHODS: Risk factors of CHD including a Polygenic Risk Score (PRS) were measured for 19 999 individuals residing in Finland in 1997, 2002, 2007 and 2012 (response rates 60%-75%). During the register-based follow-up until 2015, there were 1381 fatal and non-fatal incident CHD events. Unemployment rate, degree of urbanisation and crime rate of the municipality of residence were used as regional level social indicators. HRs were calculated using register-based antidepressant purchases as a non-reversible time-dependent covariate. RESULTS: Those having depression and in the highest quartile of PRS had somewhat higher CHD risk than predicted only by the main effects of depression and PRS (HR for interaction 1.53, 95% CI 0.95 to 2.45). Depression was moderately associated with CHD in high crime (HR 1.51, 95% CI 1.20 to 1.90) and weakly in low crime regions (HR 1.07, 95% CI 0.86 to 1.33; p value of interaction=0.087). Otherwise, we did not found evidence for interactions. CONCLUSIONS: Those having both depression and high genetic susceptibility need a special attention in healthcare for CHD.

Joint association between education and polygenic risk score for incident coronary heart disease events: a longitudinal population-based study of 26 203 men and women.

BACKGROUND: Genetic vulnerability to coronary heart disease (CHD) is well established, but little is known whether these effects are mediated or modified by equally well-established social determinants of CHD. We estimate the joint associations of the polygenetic risk score (PRS) for CHD and education on CHD events. METHODS: The data are from the 1992, 1997, 2002, 2007 and 2012 surveys of the population-based FINRISK Study including measures of social, behavioural and metabolic factors and genome-wide genotypes (N=26 203). Follow-up of fatal and non-fatal incident CHD events (N=2063) was based on nationwide registers. RESULTS: Allowing for age, sex, study year, region of residence, study batch and principal components, those in the highest quartile of PRS for CHD had strongly increased risk of CHD events compared with the lowest quartile (HR=2.26; 95% CI: 1.97 to 2.59); associations were also observed for low education (HR=1.58; 95% CI: 1.32 to 1.89). These effects were largely independent of each other. Adjustment for baseline smoking, alcohol use, body mass index, igh-density lipoprotein (HDL) and total cholesterol, blood pressure and diabetes attenuated the PRS associations by 10% and the education associations by 50%. We do not find strong evidence of interactions between PRS and education. CONCLUSIONS: PRS and education predict CHD events, and these associations are independent of each other. Both can improve CHD prediction beyond behavioural risks. The results imply that observational studies that do not have information on genetic risk factors for CHD do not provide confounded estimates for the association between education and CHD.

How voter turnout varies between different chronic conditions? A population-based register study.

BACKGROUND: While poor self-rated health is known to decrease an individual's propensity to vote, disaggregation of the components of health on turnout has thus far received only little attention. This study deepens on the understanding of such relationships by examining the association between chronic diseases and voting. METHODS: The study uses an individual-level register-based data set that contains an 11% random sample of the entire electorate in the 1999 Finnish parliamentary elections. With information on hospital discharge diagnoses and reimbursements for drugs prescribed, we identify persons with chronic hospital-treated diseases (coronary heart disease, chronic obstructive pulmonary disease (COPD) and asthma, depression, cancer, psychotic mental disease, diabetes, cerebrovascular disease, rheumatic disease, epilepsy, arthrosis, alcoholism, dementia, atherosclerosis, Parkinson's disease, other degenerative brain diseases, multiple sclerosis and kidney disease). RESULTS: After adjusting for gender, age, education, occupational class, income, partnership status, cohabitation with underaged children and hospitalisation during Election Day, neurodegenerative brain diseases had the strongest negative relationship with voting (dementia OR=0.20, 95% CI 0.18 to 0.22; others up to OR=0.70). Alcoholism (OR=0.66) and mental disorders also had a negative association (depression OR=0.91; psychotic mental disease OR=0.79), whereas cancer and COPD/asthma had a positive association (both OR=1.05). Having more than one condition at a time further decreased voting probability. CONCLUSIONS: By showing how different health conditions are related to voter turnout, this study provides essential information for identifying gaps in the potential for political participation and for further inquiries aiming to develop models that explain the link between health and voting probability.