Asian people are under-represented in population-based, clinical, and genomic research. To address this gap, we have initiated the HELIOS longitudinal cohort study, comprising comprehensive behavioural, phenotypic, and genomic measurements from 10,004 Asian men and women of Chinese, Indian or Malay background. Phenotyping has been carried out using validated approaches, that are internationally interoperable. Health record linkage enriches both baseline phenotyping and evaluation of prospective outcomes. The integrated multi-omics data include whole-genome and RNA sequencing, quantification of DNA methylation, and metabolomic profiling. Our data reveal extensive lifestyle, physiological, genomic, and molecular diversity between the distinct Asian ethnic groups, and the biological interconnectivity between functional layers. This includes characterisation of divergent patterns of genome regulation between Asian individuals, that correlate with differences in educational attainment, dietary quality, and adiposity, and which overlap transcription factors and DNA methylation sites linked to the development of diabetes and other chronic diseases. Our unique HELIOS Asian Precision Medicine cohort study represents a state-of-the art platform to enable biomedical researchers to understand the aetiology and pathogenesis of diverse disease outcomes in Asia, and to generate insights that have the potential to improve health outcomes for Asian populations globally.

B.L.C.C. receives honorarium for obesity-related presentations and/or participates in the advisory board of Novo Nordisk, Abbott Nutrition and DKSH, and all honorariums were paid to Khoo Teck Puat Hospital, Singapore. J.N. receives research funding from Astra Zeneca. J.L. participates in the advisory board of Boehringer Ingelheim and is a council member of National Council Against Drug Abuse, Singapore. G.A.M, K.E.W, and P.A.S are employees of Metabolon. L.P.Y., and Y.Z.X. are employees of Ministry of Health, Singapore. The other authors declare no competing financial interests.

This study is supported by Singapore Ministry of Health (MOH) National Medical Research Council (NMRC) under its OF-LCG funding scheme (MOH-000271-00), Singapore Translational Research (StaR) funding scheme (NMRC/StaR/0028/2017), the National Research Foundation, Singapore through the Singapore MOH NMRC and the Precision Health Research, Singapore (PRECISE) under the National Precision Medicine programme (NMRC/PRECISE/2020) and intramural funding from Nanyang Technological University, Lee Kong Chian School of Medicine and the National Healthcare Group. RNA sequencing was partially funded by i) Ministry of Education Academic Research Fund Tier 1 Grant (RS09/20), ii) A*STAR-NHMRC Joint Grant Call (A20PRb0138), iii) Start-Up Grant (awarded to M.Loh [PI]) from Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore and iv) Imperial - Nanyang Technological University Collaboration Fund (awarded to M.Loh [PI]). T.M. was funded by Deans Postdoctoral Fellowship from the Lee Kong Chian School of Medicine. This study made use of data generated by Ministry of Health (MOH) and Immigration and Checkpoints Authority (ICA). This study was supported by the Trusted Research and Real-World-Data Utilisation and Sharing Tech platform (TRUST Platform) developed by the Ministry of Health and Smart Nation and Digital Government Office, through the use of its research data analytics facilities. The views expressed are those of the author(s) are not necessarily those of the Government, MOH and ICA investigators or institutional partners. The computational work for this study was partially performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Nanyang Technological University Institutional Review Board IRB-2016-11-030

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The HELIOS phenotype and genotype data used in this manuscript are protected and are not publicly available due to data privacy regulations. Data access request can be submitted to the HELIOS Data Access Committee by emailing helios_science@ntu.edu.sg for details. For accessing de-identified National Health and Administrative records linked through TRUST, please contact TRUST platform (https://trustplatform.sg) for details.