Regional variation in health is predominantly driven by lifestyle rather than genetics

Abstract

Regional differences in health-related phenotypes have been detected between and within countries. In Scotland, regions differ for a variety of health-related traits and display differences in mean lifespan of up to 7.5 years. Both genetics and lifestyle differences are potential causes of this variation. Using data on obesity-related traits of ~11,000 Scottish individuals with genome-wide genetic information and records of lifestyle and socioeconomic factors, we explored causes of regional variation by using models that incorporate genetic and environmental information jointly. We found that variation between individuals within regions showed substantial influence of both genetic variation and family environment. Regional variation for most obesity traits was associated with lifestyle and socioeconomic variables, such as smoking, diet and deprivation which are potentially modifiable. There was limited evidence that regional differences were of genetic origin. This has important implications for healthcare policies, suggesting that inequalities can be tackled with appropriate social and economic interventions.

Assortative mating and within-spouse pair comparisons

“…Previous studies have incorporated spousal relationships in variance component models as a measure of the shared environment during adulthood [5][6][7][8] .…”

“…The WSP model involves modelling the similarities and differences of spouses, either by analysing the differences between each pair or by modelling spousal relationships as a covariate in a fixed-effect model. For example, previous studies have used the WSP model to estimate effects of the shared adulthood environment [5][6][7][8] , while the WSP model has been proposed as an approach to reduce confounding bias in aetiological research with environmental confounders likely to be strongly correlated between spouses 9 .…”

Genome-wide methylation data improves dissection of the effect of smoking on body mass index

“…Variation in obesity-related traits such as body mass index (BMI) has a complex basis with heritabilities ranging from 40 to 70% and variants detected so far explaining up to 5% of BMI variation 1 . Although the genetic component is large, studies suggest that the increase in obesity prevalence in the past decades is linked with environmental causes like changes in the diet and a more sedentary lifestyle 2,3,4,5 , but not all relevant environmental effects are accounted for in genetic studies. On top of these independent environmental effects, several studies suggest that gene-by-environment interactions also play an important role in obesity and other complex traits 2,6,7,8,9,10 and many researchers are focusing on finding interactions between specific genes and certain environments.…”

“…Inclusion of the genome-by-methylation interaction component nominally improved the model fit for weight, BMI, and waist circumference, with estimates of the interaction component over 20% of the trait variation, but the standard errors of the estimates are large. When fitting jointly the two interaction components (genome-by-smoking and genome-by-methylation) the estimates were not significant (or just nominally significant in the case of BMI).Most complex diseases have moderate heritabilities, with different environmental sources of variation, for example, lifestyle and socioeconomic differences between individuals, also contributing to disease risk5 . These diseases, particularly obesity, pose major challenges for public health and are associated with heavy economic burdens3,4,37 .…”

Neuroticism mediates the relationship between industrial history and modern‐day regional obesity levels

“…Obesity is a multifaceted health problem characterized by a range of social, psychological and genetic determinants (Hu, 2008). Although genetics explain variation in obesity proneness between individuals, there is little evidence that genetic variation can explain substantial regional differences in obesity (Amador et al, 2017). In contrast, economic adversity is likely to play a key role in explaining regional variability in health conditions like obesity (McLaren, 2007).…”