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 single-nucleotide 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 bi-directional relationship between liability to schizophrenia and tendency towards selecting a fish and plant-based diet consistent with genetic pleiotropy.
Highlights
Schizophrenia is a chronic mental disorder with typical onset in early adulthood and a lifetime risk of approximately 0.7–0.9%1
Diet Component 1 (DC1) was associated with younger age (b = −0.01, p < 0.001) (i.e., a 1-year increase in year of birth was associated with a decrease in DC1 by 0.01 standard deviations) and females were more likely to have a lower DC1 score (b = −0.38, p < 0.001) (Supplementary Table 3)
Month of questionnaire administration was significantly associated with DC1 and Diet Component 2 (DC2)
Summary
Schizophrenia is a chronic mental disorder with typical onset in early adulthood and a lifetime risk of approximately 0.7–0.9%1. The primary factor contributing to increased mortality is cardiovascular disease (CVD)[3]. Weight gain and obesity, which are common in schizophrenia[4], are important risk factors for CVD5. Evidence of shared genetic factors between schizophrenia and obesity has been reported, but not in the direction expected from epidemiological data. There is no evidence for a genetic relationship between schizophrenia and Type 2 diabetes = 0.05, p = 1.0)[7] These results imply that if genetic factors contribute to the associations between metabolic syndrome and schizophrenia, this is a likely complex relationship
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