Study Design and Genetic Instruments
The study design overview and the assumptions of an MR study are shown
in Fig. 1 . Genetic instruments for education [22], coffee
and tea consumption [23], relative fat intake [24], BMI
[25], physical activities (including three physical activity
phenotypes: overall acceleration average, self-reported
moderate-to-vigorous physical activity (MVPA) and vigorous physical
activity (VPA) [26], smoking initiation [27], lifetime smoking
index (taking into account smoking status as well as smoking duration,
heaviness, and cessation in ever smokers) [28], alcohol drinking
[27], sleep duration [29] and insomnia [30] were selected at
genome-wide significance threshold (P <
5×10–8) from corresponding genome-wide association
(GWAS) studies. Detailed information on used GWAS studies is presented
in Table 1 . Linkage disequilibrium between single-nucleotide
polymorphisms (SNPs) was assessed based on the European population of
1000 Genomes reference panel. SNPs without linkage disequilibrium
(defined by r2 < 0.01 and clump distance
>10,000 kb) were used as instrumental variables.