Genetic markers as instrumental variables: an application to child fat mass and academic achievement

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from economists. This paper examines the conditions that need to be met for genetic variants to be used as instruments. We combine the IV literature with that from genetic epidemiology, with an application to child adiposity (fat mass, determined by a dual-energy X-ray absorptiometry (DXA) scan) and academic performance. OLS results indicate that leaner children perform slightly better in school tests compared to their more adipose counterparts, but the IV findings show no evidence that fat mass affects academic outcomes.

Genetic Markers as Instrumental Variables

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from epidemiologists, economists, statisticians and social scientists. This paper examines the conditions that need to be met for genetic variants to be used as instruments. Although these have been discussed in the epidemiological, medical and statistical literature, they have not been well-defined in the economics and social science literature. The increasing availability of biomedical data however, makes understanding of these conditions crucial to the successful use of genotypes as instruments for modifiable risk factors. We combine the econometric IV literature with that from genetic epidemiology using a potential outcomes framework and review the IV conditions in the context of a social science application, examining the effect of child fat mass on academic performance.ALSPAC; Fat mass; Genetic Variants; Instrumental Variables; Mendelian Randomization; Potential Outcomes

Genetic Markers as Instrumental Variables:An Application to Child Fat Mass and Academic Achievement

The use of genetic markers as instrumental variables (IV) is receiving increasing attention from economists. This paper examines the conditions that need to be met for genetic variants to be used as instruments. We combine the IV literature with that from genetic epidemiology, with an application to child adiposity (fat mass, determined by a dual-energy X-ray absorptiometry (DXA) scan) and academic performance. OLS results indicate that leaner children perform slightly better in school tests compared to their more adipose counterparts, but the IV findings show no evidence that fat mass affects academic outcomes.Instrumental variables; Mendelian randomization; Genetic variant; Potential outcomes; Academic performance; Educational attainment; Adiposity; Fat mass; Body Mass Index; ALSPAC

Genome-wide and Mendelian randomisation studies of liver MRI yield insights into the pathogenesis of steatohepatitis

Background A non-invasive method to grade the severity of steatohepatitis and liver fibrosis is magnetic resonance imaging (MRI) based corrected T1 (cT1). We aimed to identify genetic variants influencing liver cT1 and use genetics to understand mechanisms underlying liver fibroinflammatory disease and its link with other metabolic traits and diseases. Methods First, we performed a genome-wide association study (GWAS) in 14,440 Europeans in UK Biobank with liver cT1 measures. Second, we explored the effects of the cT1 variants on liver blood tests, and a range of metabolic traits and diseases. Third, we used Mendelian randomisation to test the causal effects of 24 predominantly metabolic traits on liver cT1 measures. Results We identified six independent genetic variants associated with liver cT1 that reached GWAS significance threshold (p<5x10-8). Four of the variants (rs75935921 in SLC30A10, rs13107325 in SLC39A8, rs58542926 in TM6SF2, rs738409 in PNPLA3) were also associated with elevated transaminases and had variable effects on liver fat and other metabolic traits. Insulin resistance, type 2 diabetes, non-alcoholic fatty liver and BMI were causally associated with elevated cT1 whilst favourable adiposity (instrumented by variants associated with higher adiposity but lower risk of cardiometabolic disease and lower liver fat) was found to be protective. Conclusion The association between two metal ion transporters and cT1 indicates an important new mechanism in steatohepatitis. Future studies are needed to determine whether interventions targeting the identified transporters might prevent liver disease in at risk individuals

Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist