Cohort profile: genomic data for 26 622 individuals from the Canadian Longitudinal Study on Aging (CLSA)

Vincenzo Forgetta; Rui Li; Corinne Darmond-Zwaig; Alexandre Belisle; Cynthia Balion; Delnaz Roshandel; Christina Wolfson; Guillaume Lettre; Guillaume Pare; Andrew D Paterson; Lauren E Griffith; Chris Verschoor; Mark Lathrop; Susan Kirkland; Parminder Raina; J Brent Richards; Jiannis Ragoussis

doi:10.1136/bmjopen-2021-059021

Cohort profile: genomic data for 26 622 individuals from the Canadian Longitudinal Study on Aging (CLSA)

BMJ Open. 2022 Mar 10;12(3):e059021. doi: 10.1136/bmjopen-2021-059021.

Authors

Vincenzo Forgetta¹, Rui Li^{2

3}, Corinne Darmond-Zwaig^{2

3}, Alexandre Belisle^{2

3}, Cynthia Balion⁴, Delnaz Roshandel⁵, Christina Wolfson⁶, Guillaume Lettre⁷, Guillaume Pare⁴, Andrew D Paterson^{5

8}, Lauren E Griffith⁹, Chris Verschoor⁹, Mark Lathrop^{2

3}, Susan Kirkland¹⁰, Parminder Raina⁹, J Brent Richards^{1

6

11}, Jiannis Ragoussis^{12

3

13}

Affiliations

¹ Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montréal, QC, Canada.
² McGill Genome Centre, Department of Human Genetics, McGill University, Montréal, QC, Canada.
³ Department of Human Genetics, McGill University, Montréal, QC, Canada.
⁴ Hamilton Regional Laboratory Medicine Program, McMaster University, St. Joseph's Hospital St. Luke's Wing, Hamilton, ON, Canada.
⁵ Genetics & Genomic Biology, The Hospital for Sick Children Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
⁶ Department of Medicine & of Epidemiology and Biostatistics and Occupational Health, McGill University, Montréal, QC, Canada.
⁷ Montréal Heart Institute and Université de Montréal, Montréal, QC, Canada.
⁸ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
⁹ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹⁰ Department of Community Health and Epidemiology, Division of Geriatric Medicine, Dalhousie University, Halifax, NS, Canada.
¹¹ Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
¹² McGill Genome Centre, Department of Human Genetics, McGill University, Montréal, QC, Canada [email protected].
¹³ Department of Bioengineering, McGill University, Montréal, QC, Canada.

Abstract

Purpose: The Canadian Longitudinal Study on Aging (CLSA) Comprehensive cohort was established to provide unique opportunities to study the genetic and environmental contributions to human disease as well as ageing process. The aim of this report was to describe the genomic data included in CLSA.

Participants: A total of 26 622 individuals from the CLSA Comprehensive cohort of men and women aged 45-85 recruited between 2010 and 2015 underwent genome-wide genotyping of DNA samples collected from blood. Comprehensive quality control metrics were measured for genetic markers and samples, respectively. The genotypes were imputed to the TOPMed reference panel. Sex chromosome abnormalities were identified by copy number profiling. Classical human leukocyte antigen gene haplotypes were imputed at two-field (four-digit).

Findings to date: Of the 26 622 genotyped participants, 24 655 (92.6%) were identified as having European ancestry. These genomic data were linked to physical, lifestyle, medical, economic, environmental and psychosocial factors collected longitudinally in CLSA. The combined analysis, including CLSA genomic data, uncovered over 100 novel loci associated with key parameters to define glaucoma. The CLSA genomic dataset validated the contribution of a polygenic risk score to screen individuals with high fracture risk. It is also a valuable resource to directly identify common genetic variations associated with conditions related to complex traits. Taking advantage of the comprehensive interview and physical information collected in CLSA, this genomic dataset has been linked to psychosocial factors to investigate both the independent and interactive effects on cardiovascular disease.

Future plans: The CLSA overall is ongoing. Follow-up data will continue to be collected from participants in the current genomic subcohort, including the DNA methylation and metabolomic data. Ongoing studies focus on elucidating the role of genetic factors in cognitive decline and cardiovascular diseases. This genomic data resource is available on request through the CLSA data access application process.

Keywords: CLSA; HLA; aging; genome-wide genotyping.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging* / psychology
Canada
Female
Genomics
Glaucoma*
Humans
Longitudinal Studies
Male