Open AccessThe structural origin of metabolic quantitative diversity
Author(s) -
S. Koshiba,
Ikuko N. Motoike,
Kazuyuki Kojima,
Takanori Hasegawa,
Matsuyuki Shirota,
Tomo Saito,
Daisuke Saigusa,
Inaho Danjoh,
Fumiki Katsuoka,
Soichi Ogishima,
Yosuke Kawai,
Yumi Yamaguchi-Kabata,
Miyuki Sakurai,
Sachiko Hirano,
Junichi Nakata,
Hozumi Motohashi,
Atsushi Hozawa,
Shinichi Kuriyama,
Naoko Minegishi,
Masao Nagasaki,
Takako Toda,
Nobuo Fuse,
Hideyasu Kiyomoto,
Junichi Sugawara,
Yôichi Suzuki,
Shigeo Kure,
Nobuo Yaegashi,
Osamu Takahashi,
Kengo Kinoshita,
Jun Yasuda,
Masayuki Yamamoto
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep31463
Subject(s) - diversity (politics) , computational biology , evolutionary biology , computer science , data science , biology , anthropology , sociology
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.