While international efforts have characterized genetic variation in millions of individuals, the interplay of environmental, social, cultural, and genetic factors is poorly understood for most worldwide populations. The province of Quebec in Canada has been the site of numerous genetic studies, often focusing on individual Mendelian diseases in founder sub-populations. Here, we profiled and analyzed genome-wide genotyped variation in 29,337 Quebec residents from the large population-based cohort CARTaGENE (CaG), including rich phenotype and environmental data. We also sequenced the whole-genome of 2,173 CaG participants, including 163 and 132 individuals with grandparents born in Haiti and Morocco, respectively. We use this genetic information to gain insight into Quebec’s demography and to help interpret the potential significance of variants identified in clinically important genes. We built an imputation panel by phasing the CaG whole-genome sequence data and showed, using genome-wide association studies (GWAS), how it improves the discovery of phenotype-genotype associations in this population. We provide allele frequency information and GWAS results through dedicated and publicly available websites. The genetic data, paired with phenotypic and environmental information, is also available for research use upon scientific and ethical review.

The authors have declared no competing interest.

This research has been conducted using Data and Biosamples from CARTaGENE (https://cartagene.qc.ca/en). This work has been made possible through financial support from Genome Quebec (Ministere de l’Economie de l’Innovation et de l’Energie), the Canadian Partnership Against Cancer and Health Canada. Grants from Genome Quebec, Genome Canada and CHU Ste-Justine supported the GenoRef-Q whole-genome sequencing project. This research was enabled in part by support provided by Calcul Quebec (https://www.calculquebec.ca/) and the Digital Research Alliance of Canada (alliancecan.ca). Work in the Lettre lab is funded by the Canadian Institutes of Health Research (Projects #426541 and #486808), the Canada Research Chair program, and the Montreal Heart Institute Foundation (G.L.); Fondation Courtois and FRQS-Junior 2 (M.T.); Work in the Gravel lab was funded by the Canada Research Chair program, CIHR project grant 437576 and NSERC discovery grant (S. Gravel); S.A.G.T. was funded by a Junior 2 award from the Fonds de Recherche du Québec - Santé (FRQS; https://frq.gouv.qc.ca). Work in the Gagliano Taliun lab is funded by the Alzheimer Society Research Program by the Alzheimer Society of Canada and co-funding by the Canadian Institutes of Health Research - Institute of Aging (Funding Reference Number 189919), as well as by additional support by the Canadian Institutes of Health Research (PJT 183817, PJT 191687 and AD6 192920); FRQS-Junior 1 (C.B.); FRQS Senior (A.-M.L.); National Institutes of Health grant numbers R35-CA197449, R01-HL163560, U01HG012064 (H.Z.). J.H. was a FRQS Junior 2 fellow, work was funded by Montreal Heart Institute Foundation, NSERC Discovery Grant (RGPIN-2022-04262) (J.H.). This research was made possible using the data/biospecimens collected by the Canadian Longitudinal Study on Aging (CLSA). Funding for the Canadian Longitudinal Study on Aging (CLSA) is provided by the Government of Canada through the Canadian Institutes of Health Research (CIHR) under grant reference: LSA 94473 and the Canada Foundation for Innovation, as well as the following provinces, Newfoundland, Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia. This research has been conducted using the CLSA datasets: baseline comprehensive dataset - version 7.0 and Genome-wide genetic data - version 3.0 under Application Number 23ME002. The CLSA is led by Drs. Parminder Raina, Christina Wolfson and Susan Kirkland. The opinions expressed in this manuscript are the author’s own and do not reflect the views of the Canadian Longitudinal Study on Aging.

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:

CARTaGENE (CaG) is approved by the Ethics Committee of the CHU Ste-Justine. A local Institutional Review Board (IRB) for each investigator involved in this study has also approved genetic analyses of the CaG data.

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

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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