TY - JOUR
T1 - The structural origin of metabolic quantitative diversity
AU - Koshiba, Seizo
AU - Motoike, Ikuko
AU - Kojima, Kaname
AU - Hasegawa, Takanori
AU - Shirota, Matsuyuki
AU - Saito, Tomo
AU - Saigusa, Daisuke
AU - Danjoh, Inaho
AU - Katsuoka, Fumiki
AU - Ogishima, Soichi
AU - Kawai, Yosuke
AU - Yamaguchi-Kabata, Yumi
AU - Sakurai, Miyuki
AU - Hirano, Sachiko
AU - Nakata, Junichi
AU - Motohashi, Hozumi
AU - Hozawa, Atsushi
AU - Kuriyama, Shinichi
AU - Minegishi, Naoko
AU - Nagasaki, Masao
AU - Takai-Igarashi, Takako
AU - Fuse, Nobuo
AU - Kiyomoto, Hideyasu
AU - Sugawara, Junichi
AU - Suzuki, Yoichi
AU - Kure, Shigeo
AU - Yaegashi, Nobuo
AU - Tanabe, Osamu
AU - Kinoshita, Kengo
AU - Yasuda, Jun
AU - Yamamoto, Masayuki
N1 - Funding Information:
We thank all the volunteers who participated in this study. We thank members of ToMMo at Tohoku University for the contribution to the establishment of the genome cohort and biobank and for help in the metabolome analyses (http://www.megabank.tohoku.ac.jp/english/a141201). This work was supported in part by the Tohoku Medical Megabank Project from AMED and MEXT.
Publisher Copyright:
© The Author(s) 2016.
PY - 2016/8/16
Y1 - 2016/8/16
N2 - Relationship between structural variants of enzymes and metabolic phenotypes in human population was investigated based on the association study of metabolite quantitative traits with whole genome sequence data for 512 individuals from a population cohort. We identified five significant associations between metabolites and non-synonymous variants. Four of these non-synonymous variants are located in enzymes involved in metabolic disorders, and structural analyses of these moderate non-synonymous variants demonstrate that they are located in peripheral regions of the catalytic sites or related regulatory domains. In contrast, two individuals with larger changes of metabolite levels were also identified, and these individuals retained rare variants, which caused non-synonymous variants located near the catalytic site. These results are the first demonstrations that variant frequency, structural location, and effect for phenotype correlate with each other in human population, and imply that metabolic individuality and susceptibility for diseases may be elicited from the moderate variants and much more deleterious but rare variants.
AB - Relationship between structural variants of enzymes and metabolic phenotypes in human population was investigated based on the association study of metabolite quantitative traits with whole genome sequence data for 512 individuals from a population cohort. We identified five significant associations between metabolites and non-synonymous variants. Four of these non-synonymous variants are located in enzymes involved in metabolic disorders, and structural analyses of these moderate non-synonymous variants demonstrate that they are located in peripheral regions of the catalytic sites or related regulatory domains. In contrast, two individuals with larger changes of metabolite levels were also identified, and these individuals retained rare variants, which caused non-synonymous variants located near the catalytic site. These results are the first demonstrations that variant frequency, structural location, and effect for phenotype correlate with each other in human population, and imply that metabolic individuality and susceptibility for diseases may be elicited from the moderate variants and much more deleterious but rare variants.
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U2 - 10.1038/srep31463
DO - 10.1038/srep31463
M3 - Article
AN - SCOPUS:84982221256
SN - 2045-2322
VL - 6
JO - Scientific Reports
JF - Scientific Reports
M1 - 31463
ER -
