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Rigorous Evaluation of Genetic and Epigenetic Effects on Clinical Laboratory Measurements Using Japanese Monozygotic Twins.

Jumpei Taniguchi, Tatsuo Masuda, Yoshinori Iwatani, Kenichi Yamamoto, Norio Osaka Twin Res Grp, Norio Sakai, Yukinori Okada, Mikio Watanabe

Clinical genetics(2023)

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Abstract
The investigation of environmental effects on clinical measurements using individual samples is challenging because their genetic and environmental factors are different. However, using monozygotic twins (MZ) makes it possible to investigate the influence of environmental factors as they have the same genetic factors within pairs because the difference in the clinical traits within the MZ mostly reflect the influence of environmental factors. We hypothesized that the within-pair differences in the traits that are strongly affected by genetic factors become larger after genetic risk score (GRS) correction. Using 278 Japanese MZ pairs, we compared the change in within-pair differences in each of the 45 normalized clinical measurements before and after GRS correction, and we also attempted to correct for the effects of genetic factors to identify Cytosine-phosphodiester-Guanine (CpG) sites in DNA sequences with epigenetic effects that are regulated by genetic factors. Five traits were classified into the high heritability group, which was strongly affected by genetic factors. CpG sites could be classified into three groups: regulated only by environmental factors, regulated by environmental factors masked by genetic factors, and regulated only by genetic factors. Our method has the potential to identify trait-related methylation sites that have not yet been discovered.
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Key words
environmental factor,epigenetic factor,genetic factor,laboratory test,monozygotic twin
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