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Article History

Received: 18 December 2023

Accepted: 16 July 2024

First Online: 30 September 2024

Acknowledgements

: The authors would like to thank all of the individuals who participated in the parent studies and all the researchers, clinicians, technicians and administrative staff for their valuable contribution to the studies. A list of the PAGE senior investigators can be found at . A list of participating MESA investigators and institutes can be found at . Participants in the INTERVAL RCT were recruited with the active collaboration of NHS Blood and Transplant England ( ), which has supported field work and other elements of the trial. A complete list of the investigators and contributors to the INTERVAL trial is provided in reference [*]. The academic coordinating centre would also like to thank blood donor centre staff and blood donors for participating in the INTERVAL trial. WGS for the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung and Blood Institute (NHLBI). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.*Di Angelantonio E, Thompson SG, Kaptoge SK, Moore C, Walker M, Armitage J, Ouwehand WH, Roberts DJ, Danesh J, INTERVAL Trial Group. Efficiency and safety of varying the frequency of whole blood donation (INTERVAL): a randomised trial of 45 000 donors. Lancet. 2017 Nov 25;390(10110):2360–2371

: The summary statistics of multi-ethnic type 2 diabetes GWAS of MVP, DIAMANTE, Biobank Japan and other studies are available from The database of Genotypes and Phenotypes (dbGaP) under accession number phs001672.v3.p1. MESA genetic, proteome and covariate data can be accessed through dbGaP under phs000209.v13.p3. All code is available on GitHub ( ).

: This research is supported by the University of Hawaiʻi Cancer Center and The Hawaiʻi Advanced Training in Artificial Intelligence for Precision Nutrition Science Research (AIPrN) (T32DK137523). LWu is also supported by V Foundation V Scholar Award, NCI R01CA263494 and NHGRI/NIMHD U54HG013243. The Population Architecture Using Genomics and Epidemiology (PAGE) program is funded by the National Human Genome Research Institute (NHGRI), supported by R01HG010297. WGS for ‘NHLBI TOPMed: Multi-Ethnic Study of Atherosclerosis (MESA)’ (phs001416.v1.p1) was performed at the Broad Institute of MIT and Harvard (3U54HG003067–13S1). SOMAscan proteomics for NHLBI TOPMed: Multi-Ethnic Study of Atherosclerosis (MESA) (phs001416.v1.p1) was performed at the Broad Institute and Beth Israel Proteomics Platform (HHSN268201600034I). Centralised read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626–02S1). Phenotype harmonisation, data management, sample-identity quality control and general study coordination were provided by the TOPMed Data Coordinating Center (3R01HL-120393–02S1) and TOPMed MESA Multi-Omics (HHSN2682015000031/HSN26800004). The MESA projects are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. The Multi-Ethnic Study of Atherosclerosis (MESA) projects are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163,75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1TR001881, DK063491 and R01HL105756. Supported in part by the National Institutes of Health, National Heart, Lung, and Blood Institute (NHLBI) contract 1R01HL15185, R01DK081572 and the National Institute of Diabetes and Digestive and Kidney Diseases contract UM1DK078616. DNA extraction and genotyping were co-funded by the National Institute for Health Research (NIHR), the NIHR BioResource ( ) and the NIHR Cambridge Biomedical Research Centre (BRC-1215–20014). The academic coordinating centre for INTERVAL was supported by core funding from the NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014–10024), UK Medical Research Council (MR/L003120/1), British Heart Foundation (SP/09/002; RG/13/13/30194; RG/18/13/33946) and NIHR Cambridge BRC (BRC-1215–20014). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.

: LWu provided consulting service to Pupil Bio Inc., reviewed manuscripts for Gastroenterology Report not related to this study, and received honorarium. LMR is a consultant for the NHLBI Trans-Omics for Precision Medicine (TOPMed) consortium Administrative Coordinating Center (through Westat). QQ is a member of the editorial board of Diabetologia . PD and SB received grants from Regeneron Genetics Center LLC. The other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.

: LWu conceived and designed the study. SL developed the protein genetic prediction models. SL, JZ and HZ performed statistical analyses. JZ performed drug-repurposing analysis. CW and HX contributed to the fine-mapping analyses. HZ performed IPA analysis. SL wrote the initial draft manuscript with critical additions and inputs from JZ and LWu. BFD, XG, PD, RPT, YL, WCJ, KDT, AWM, MOG, REG, CBC, Y-DIC, HH, CAH, CRG, LL, DVC, LMR, LWi, LLM, KEN, KLY, RJL, SB, TM, UP, CK, APR, BY, EB, QS, MRR, JBE-T, MLD, QQ, NM, CL, YD, AM, JBM, SSR and JIR conducted the experiment, contributed materials and provided valuable feedback for revising and reviewing the manuscript. All authors contributed to the manuscript revision. All authors read and approved the final manuscript. LWu is the guarantor of this work.

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