Yu, Gechang
Tam, Claudia H. T.
Shi, Mai
Hughes, Alice E.
Huang, Chuiguo
Deng, Yuzhi
Weedon, Michael N.
Lim, Cadmon K. P.
Wang, Chi Chiu
Chan, Juliana C. N.
Tam, Wing Hung
Lowe, William Jr
Freathy, Rachel M.
Oram, Richard A.
Ma, Ronald C. W. https://orcid.org/0000-0002-2795-714X
Funding for this research was provided by:
National Institute of Diabetes and Digestive and Kidney Diseases (R01-HD34243)
the RGC Area of Excellence Scheme (AoE/M-401/24-R)
National Institute of Child Health and Human Development (R01-HD34242)
National Human Genome Research Institute (HG-004415)
National Institute for Health and Care Research Exeter Biomedical Research Centre
Wellcome Senior Research Fellowship (WT220390)
General Research Fund of the Research Grants Council of the Hong Kong SAR, China (CUHK 473408)
General Research Fund of the Research Grants Council of the Hong Kong SAR, China (471713)
General Research Fund of the Research Grants Council of the Hong Kong SAR, China (14118718)
General Research Fund of the Research Grants Council of the Hong Kong SAR, China (14102719)
Research Grants Council Research Impact Fund (R4012-18)
Wellcome Trust (WT220390)
Chinese Universtity of Hong Kong International Joint Supervision of PhD Students Scheme
University Grants Committee Research Grants Matching Scheme
Article History
Received: 10 June 2025
Accepted: 4 December 2025
First Online: 3 February 2026
Acknowledgements
: We thank the HAPO Study steering committee for initiating and conducting the original study, and for their kind help and support. We are also grateful to all the study participants for their contribution. Special thanks are extended to all medical and nursing staff at all participating centres for their dedication and professionalism. We thank all team members for their kind assistance, and their efforts on the recruitment of participants and data collection. We acknowledge dbGaP for making the genotype data from the HAPO Study available for analysis.
: Genotype and clinical data from HAPO centres other than Hong Kong were obtained from the database of Genotypes and Phenotypes (dbGaP; ) with accession number ‘phs000096.v4.p1’. The GWAS summary statistics can be downloaded from (type 2 diabetes), (maternal and fetal genetically determined birthweight), (insulin secretion) and (insulin sensitivity).
: The codes for all the analysis in this study are stored in GitHub The following software and packages were used for data analysis:R packages: coloc: ; meta: ; metapower: ; LDlinkR: ; TwoSampleMR: ; MATLAB toolbox: Mediation:
: This work was funded by the RGC Area of Excellence Scheme (AoE/M-401/24-R), the RGC Research Impact Fund (R4012–18), and the University Grants Committee Research Grants Matching Scheme. RCWM acknowledges support from the International Joint Supervision of PhD Students Scheme from the Office of Academic Links of the Chinese University of Hong Kong. The follow-up of the HAPO Study at the Hong Kong field centre was supported by the General Research Fund of the Research Grants Council of the Hong Kong SAR, China (CUHK 473408, 471713, 14118718, 14102719). The HAPO Study was funded by the National Institute of Child Health and Human Development (grant no. R01-HD34242) and the National Institute of Diabetes and Digestive and Kidney Diseases (grant no. R01-HD34243). HAPO genetics data was generated with the support of National Human Genome Research (grant no. HG-004415). RMF is supported by a Wellcome Senior Research Fellowship (WT220390). This study was supported by the National Institute for Health and Care Research Exeter Biomedical Research Centre. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. This research was funded, in part, by the Wellcome Trust (grant no. WT220390). The funding sources do not have any role in the design, interpretation of the study, or the decision to publish the results.
: RCWM is a member of the editorial board of Diabetologia . The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.
: The study was conceived by GY, CHTT, RAO and RCWM. CHTT, CKPL, JCNC, WHT, WL and RCWM were responsible for study infrastructure and logistics. Funding was acquired by WHT, WL Jnr and RCWM. CHTT, WHT and RCWM were responsible for data collection and curation. GY, CHTT, MS, AH, CH, YD, MNW, CKPL, CCW, WHT, RMF, RAO and RCWM performed data analysis and interpretation. The manuscript was drafted by GY, CHTT, AEH, RMF, RAO and RCWM; GY, CHTT, AEH, MS, CH, YD, MNW, CKPL, CCW, JCNC, WHT, WL Jnr, RMF, RAO and RCWM contributed to the writing of the manuscript and critical revisions. All authors approved the final version of the article to be published. RCWM is the guarantor of this work and takes responsibility for the integrity of the data and the accuracy of the data analysis.