Genome-wide association study of dietary intake in the UK biobank study and its associations with schizophrenia and other traits

Abstract

Motivated by observational studies that report associations between schizophrenia and traits, such as poor diet, increased body mass index and metabolic disease, we investigated the genetic contribution to dietary intake in a sample of 335,576 individuals from the UK Biobank study. A principal component analysis applied to diet question item responses generated two components: Diet Component 1 (DC1) represented a meat-related diet and Diet Component 2 (DC2) a fish and plant-related diet. Genome-wide association analysis identified 29 independent singlenucleotide polymorphisms (SNPs) associated with DC1 and 63 SNPs with DC2. Estimated from over 35,000 3rd-degree relative pairs that are unlikely to share close family environments, heritabilities for both DC1 and DC2 were 0.16 (standard error (s.e.) = 0.05). SNP-based heritability was 0.06 (s.e. = 0.003) for DC1 and 0.08 (s.e = 0.004) for DC2. We estimated significant genetic correlations between both DCs and schizophrenia, and several other traits. Mendelian randomisation analyses indicated a negative uni-directional relationship between liability to schizophrenia and tendency towards selecting a meat-based diet (which could be direct or via unidentified correlated variables), but a bidirectional relationship between liability to schizophrenia and tendency towards selecting a fish and plant-based diet consistent with genetic pleiotropy.

Causal Associations Between Modifiable Risk Factors and the Alzheimer's Phenome

“…We obtained genomewide association study (GWAS) summary statistics (GWAS-SS) for each exposure and outcome of interest (Table 1). Modifiable risk factors included alcohol consumption, 9 the alcohol use disorder identification test (AUDIT), 10 moderate-vigorous physical activity (MVPA), 11 lipid traits, 12 systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), 13 type 2 diabetes (T2D), 14 body mass index (BMI), 15 meat-related diet and a fishand plant-related diet, 16 depression, 17 insomnia symptoms, 18 sleep duration, 19 social isolation, 20 smoking initiation, 9 cigarettes per day, 9 educational attainment, 21 and hearing difficulty. 22 These summary statistics were used to generate PRS and as the exposures in the MR analyses.…”

Exploring a Region on Chromosome 8p23.1 Displaying Positive Selection Signals in Brazilian Admixed Populations: Additional Insights Into Predisposition to Obesity and Related Disorders

“…In Table 2 , we present the list of 17 genes that have been linked to diet patterns in large association studies and are located in the candidate region on ch 8p23.1. Seven of these large studies included Hispanic, Native-American, and Caribbean populations ( Comuzzie et al, 2012 ; Divers et al, 2017 ; Pulit et al, 2019 ; Rask-Andersen et al, 2019 ; Niarchou et al, 2020 ; Schlauch et al, 2020 ; Vujkovic et al, 2020 ), and three contained association signals in the ERI1 gene ( Pulit et al, 2019 ; Rask-Andersen et al, 2019 ; Schlauch et al, 2020 ), which is located within the region and was determined to possess the greatest degree of positive selection in admixed Brazilians in our previous work ( Secolin et al, 2019 ).…”

Association between polygenic propensity for a psychiatric disorder and nutrient intake

“…A recent UK Biobank study found significant genetic correlations between schizophrenia and two diet groups, one representing a meat-related diet and the other a fish and plant-related diet (Niarchou et al 2020). This spurred our in-depth investigation of the association between polygenic scores for psychiatric disorders and nutrient intake.…”

“…Despite i) the phenotypic evidence for an association between psychiatric disorders and disturbances in nutrient intake and ii) the heritability of both, little empirical attention has been given to understanding their genetic overlap. A recent UK Biobank study found significant genetic correlations between schizophrenia and two diet groups - one representing a meat-related diet and the other a fish and plant-related diet (Niarchou et al 2020). This study highlights the need for more genetic studies to better understand the relationship between psychiatric disorders and nutrient intake.…”