Poster Presentation GENEMAPPERS 2026

New genome-wide data for >7,400 Australians integrated with large-scale longitudinal health, socioeconomic, behaviour and linked medical data within the 45 and Up Study (#53)

Hamzeh Mesrian Tanha 1 , David Goldsbury 1 , Greer Dawson 2 , Kerrin Bleicher 2 3 , Alison Cowle 2 , Martin McNamara 2 , Anne E Cust 1 , Nicholas G Martin 4 , Julia Steinberg 1
  1. The Daffodil Centre, The University of Sydney, and Cancer Council NSW, Sydney, Australia, Sydney
  2. Sax Institute, Sydney, NSW, Australia, Sydney
  3. Deakin University, Melbourne, VIC, Australia, Melbourne
  4. QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia , Brisbane

Large-scale cohort studies linking genomic and longitudinal health/medical data are highly valuable for insights into health and disease. In particular, the 45 and Up Study[1] includes 267,357 participants age 45+ years recruited in 2005-2009, with extensive information on health and sociodemographic characteristics[2-3]. As part of the Australian Cancer Risk Study, we invited 30,541 participants to provide a DNA sample, including a randomly selected sub-cohort (n=9,986), and all participants diagnosed with prostate, breast, melanoma and colorectal cancer who were alive in October 2021 (identified via linked NSW Cancer Registry data).

Overall, 8,311 participants consented (27%), with higher consent among individuals age <85, with university education, excellent self-reported health, and higher household incomes (p<0.0001, adjusting for a wide range of health and sociodemographic characteristics). We then generated new genomic data for 7,408 participants using low-coverage whole-genome sequencing (minimum=0.4X, median coverage=0.8X) and genotype imputation (GLIMPSE2, using Gencove’s well-established analysis pipeline).

Following in-depth sample- and variant-level quality checks (QC), we retained a final high-quality genomic dataset of 6,741 participants, including 6,545 unrelated individuals with inferred European genetic ancestry.

Among the 6,545 unrelated European-ancestry participants, minor allele frequencies of >955K post-QC HapMap3 variants were highly correlated with European-ancestry 1000 Genomes reference data (r=0.998, p<10-10).

Considering key examples of cancer polygenic risk scores (PGS; breast: PGS313[4]; prostate: PGS269[5], PGS451, PGS400[6]; melanoma: PGS68[7]; colorectal: PGS205[8], PGS252[8-9]), we found that 62-76% of variants passed QC and were generally imputed with high confidence (genotype probability >90% in ≥90% participants). The risk prediction performance of these PGS in our new data was comparable to previous studies for prostate, breast and melanoma (area-under-the-ROC-curve 0.66-0.68, 0.62, 0.64, respectively), but slightly reduced for colorectal cancer (~0.57 vs ~0.62[6]).

In conclusion, we present a major newly generated high-quality Australian genomics resource, readily integrated with longitudinal linked health data from the 45 and Up Study.

  1. [1] Bleicher K, Summerhayes R, Baynes S, et al. Cohort Profile Update: The 45 and Up Study. Int J Epidemiol. 2023;52(1):e92-e101. doi:10.1093/ije/dyac104
  2. [2] We thank the Centre for Health Record Linkage (CHeReL, www.cherel.org.au) for the provision of linked data.
  3. [3] Secure data access was provided through the Sax Institute’s Secure Unified Research Environment (SURE).
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