NDLI: Constructing an atlas of associations between polygenic scores from across the human phenome and circulating metabolic biomarkers

Content Provider	Directory of Open Access Journals (DOAJ)
Author	Tom R. Gaunt George Davey Smith Tom G. Richardson Si Fang Michael V. Holmes
Abstract	Background: Polygenic scores (PGS) are becoming an increasingly popular approach to predict complex disease risk, although they also hold the potential to develop insight into the molecular profiles of patients with an elevated genetic predisposition to disease. Methods: We sought to construct an atlas of associations between 125 different PGS derived using results from genome-wide association studies and 249 circulating metabolites in up to 83,004 participants from the UK Biobank. Results: As an exemplar to demonstrate the value of this atlas, we conducted a hypothesis-free evaluation of all associations with glycoprotein acetyls (GlycA), an inflammatory biomarker. Using bidirectional Mendelian randomization, we find that the associations highlighted likely reflect the effect of risk factors, such as adiposity or liability towards smoking, on systemic inflammation as opposed to the converse direction. Moreover, we repeated all analyses in our atlas within age strata to investigate potential sources of collider bias, such as medication usage. This was exemplified by comparing associations between lipoprotein lipid profiles and the coronary artery disease PGS in the youngest and oldest age strata, which had differing proportions of individuals undergoing statin therapy. Lastly, we generated all PGS–metabolite associations stratified by sex and separately after excluding 13 established lipid-associated loci to further evaluate the robustness of findings. Conclusions: We envisage that the atlas of results constructed in our study will motivate future hypothesis generation and help prioritize and deprioritize circulating metabolic traits for in-depth investigations. All results can be visualized and downloaded at http://mrcieu.mrsoftware.org/metabolites_PRS_atlas. Funding: This work is supported by funding from the Wellcome Trust, the British Heart Foundation, and the Medical Research Council Integrative Epidemiology Unit.
e-ISSN	2050084X
DOI	10.7554/eLife.73951
Journal	eLife
Volume Number	11
Language	English
Publisher	eLife Sciences Publications Ltd
Publisher Date	2022-01-01
Publisher Place	United Kingdom
Access Restriction	Open
Subject Keyword	Medicine Science Biology (general) Polygenic Risk Scores Metabolic Signatures Mendelian Randomization Circulating Biomarkers
Content Type	Text
Resource Type	Article

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in