Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study

Hozawa, Atsushi; Tanno, Kozo; Nakaya, Naoki; Nakamura, Tomohiro; Tsuchiya, Naho; Hirata, Takumi; Narita, Akira; Kogure, Mana; Nochioka, Kotaro; Sasaki, Ryohei; Takanashi, Nobuyuki; Otsuka, Kotaro; Sakata, Kiyomi; Kuriyama, Shinichi; Kikuya, Masahiro; Takahashi, Osamu; Sugawara, Junichi; Suzuki, Kichiya; Suzuki, Yôichi; Kodama, Eiichi N.; Fuse, Nobuo; Kiyomoto, Hideyasu; Tomita, Hiroaki; Uruno, Akira; Hamanaka, Yohei; Metoki, Hirohito; Ishikuro, Mami; Obara, Taku; Kobayashi, Tomoko; Kitatani, Kazuyuki; Toda, Takako; Ogishima, Soichi; Satoh, Mamoru; Ohmomo, Hideki; Tsuboi, Akito; Egawa, Shinichi; Ishii, Tadashi; Itō, Kiyoshi; Ito, Sadayoshi; Taki, Yasuyuki; Minegishi, Naoko; Ishii, Naoto; Nagasaki, Masao; Igarashi, Kazuhiko; Koshiba, S.; Shimizu, Ritsuko; Tamiya, Gen; Nakayama, Keiko; Motohashi, Hozumi; Yasuda, Jun; Shimizu, Atsushi; Hachiya, Tsuyoshi; Shiwa, Yuh; Tominaga, Teiji; Tanaka, Hiroshi; Oyama, Kotaro; Tanaka, Ryoichi; Kawame, Hiroshi; Fukushima, Akimune; Ishigaki, Yasushi; Tokutomi, Tomoharu; Osumi, Noriko; Kobayashi, Tadao; Nagami, Fuji; Hashizume, Hiroaki; Arai, Tomohiko; Kawaguchi, Yoshio; Higuchi, Shinichi; Sakaida, Masaki; Endo, Ryujin; Nishizuka, Satoshi; Tsuji, Ichiro; Hitomi, Jiro; Nakamura, Motoyuki; Ogasawara, Kuniaki; Yaegashi, Nobuo; Kinoshita, Kengo; Kure, Shigeo; Sakai, Akio; Kobayashi, Seiichiro; Sobue, Kenji; Sasaki, Makoto; Yamamoto, Masayuki

doi:10.2188/jea.je20190271

Cited by 100 publications

(94 citation statements)

References 32 publications

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“…Study subjects in the Japanese cohort. In the discovery cohort, we performed a GWAS in Japanese sporadic ALS cases from the Japanese Consortium for ALS research (JaCALS) 32 and in normal controls from the Tohoku Medical Megabank Project (TMM) 33,34 . In the replication cohort, we obtained DNA from ALS patients registered by BioBank Japan 35,36 and normal controls registered in the Pharma SNP Consortium.…”

Section: Methodsmentioning

confidence: 99%

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A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

et al. 2020

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Amyotrophic lateral sclerosis (ALS) is a devastating progressive motor neuron disease that affects people of all ethnicities. Approximately 90% of ALS cases are sporadic and thought to have multifactorial pathogenesis. To understand the genetics of sporadic ALS, we conducted a genome-wide association study using 1,173 sporadic ALS cases and 8,925 controls in a Japanese population. A combined meta-analysis of our Japanese cohort with individuals of European ancestry revealed a significant association at the ACSL5 locus (top SNP p = 2.97 × 10−8). We validated the association with ACSL5 in a replication study with a Chinese population and an independent Japanese population (1941 ALS cases, 3821 controls; top SNP p = 1.82 × 10−4). In the combined meta-analysis, the intronic ACSL5 SNP rs3736947 showed the strongest association (p = 7.81 × 10−11). Using a gene-based analysis of the full multi-ethnic dataset, we uncovered additional genes significantly associated with ALS: ERGIC1, RAPGEF5, FNBP1, and ATXN3. These results advance our understanding of the genetic basis of sporadic ALS.

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Section: Methodsmentioning

confidence: 99%

“…Japanese controls for the discovery study. The control cohort was the prospective cohort of the Tohoku Medical Megabank Project (TMM) 33,34 . From these TMM samples, we used 9,924 samples genotyped with Illumina HumanOmniExpressExome-8 BeadChips (version 1.2-B) at RIKEN.…”

Section: Methodsmentioning

confidence: 99%

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

et al. 2020

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“…Study population. The TMM project conducts population-based prospective cohort studies with more than 150,000 participants in Japan 63,64 . The participants in this cohort project were not selected based on any outcome or disease.…”

Section: Methodsmentioning

confidence: 99%

Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population

et al. 2020

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We performed a metabolome genome-wide association study for the Japanese population in the prospective cohort study of Tohoku Medical Megabank. By combining whole-genome sequencing and nontarget metabolome analyses, we identified a large number of novel associations between genetic variants and plasma metabolites. Of the identified metabolite-associated genes, approximately half have already been shown to be involved in various diseases. We identified metabolite-associated genes involved in the metabolism of xenobiotics, some of which are from intestinal microorganisms, indicating that the identified genetic variants also markedly influence the interaction between the host and symbiotic bacteria. We also identified five associations that appeared to be female-specific. A number of rare variants that influence metabolite levels were also found, and combinations of common and rare variants influenced the metabolite levels more profoundly. These results support our contention that metabolic phenotyping provides important insights into how genetic and environmental factors provoke human diseases.

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“…TMM was launched in the aftermath of the Great East Japan Earthquake of March 11, 2011, and aims to contribute to the realization of personalized healthcare and medicine through the construction of an integrated biobank consisting of clinical information, genome and omics data, and biospecimens. TMM follows a prospective cohort design, targeting a total of 150,000 participants from the general population of the Miyagi and Iwate Prefectures (Hozawa et al 2020).…”

Section: Study Populationmentioning

confidence: 99%

Genomic Heritabilities and Correlations of 17 Traits Related to Obesity and Associated Conditions in the Japanese Population

Gervais

Ueno

Kawai

et al. 2020

G3 Genes|Genomes|Genetics

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Over the past few decades, obesity has become a public health issue of global concern. Even though disparities exist between human populations, e.g., the higher liver fat content of the Japanese despite a lower body mass index (BMI), studies on the genetics of obesity still largely focus on populations of European descent, leading to a dearth of genetic data on non-European populations. In this context, this study aimed to establish a broad picture of the genetic attributes of the Japanese population, by examining a representative sample of 18,889 individuals participating in the Tohoku Medical Megabank Project cohort. We applied linear mixed model methods to 17 traits related to obesity and associated diseases to estimate the heritabilities explained by common genetic variants and the genetic correlations between each pair of traits. These analyses allowed us to quantify the SNP heritability of health indicators such as BMI (0.248 ± 0.032) and HDL cholesterol (0.324 ± 0.031), and to provide one of the few estimates of the SNP heritability of cystatin C in unrelated individuals (0.260 ± 0.025). We discuss potential differences between the Japanese and people of European ancestry with respect to the genetic correlations between urinary biomarkers and adiposity traits, for which large estimates were obtained. For instance, the genetic correlations between urine potassium level and the values for weight, BMI, waist circumference, and waist-to-height ratio ranged from 0.290 to 0.559, much higher than the corresponding estimates in the UK Biobank.

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Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process which may lead to differences between this version and the Version of Record.

Cited by 100 publications

References 32 publications

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

A multi-ethnic meta-analysis identifies novel genes, including ACSL5, associated with amyotrophic lateral sclerosis

Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population

Genomic Heritabilities and Correlations of 17 Traits Related to Obesity and Associated Conditions in the Japanese Population

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