Genotyping and population characteristics of the China Kadoorie Biobank

Walters, Robin G.; Millwood, Iona Y.; Lin, Kuang; Valle, Dan Schmidt; McDonnell, Pandora; Hacker, Alex; Avery, Daniel; Edris, Ahmed; Fry, Hannah; Cai, Na; Kretzschmar, Warren W.; Ansari, Azim; Lyons, Paul; Collins, Rory; Donnelly, Peter; Hill, Michael; Pető, Richárd; Shen, Hongbing; Jin, Xin; Nie, Chao; Xu, Xun; Guo, Yu; Yu, Canqing; Lv, Jun; Clarke, Robert; Li, Liming; Chen, Zhengming

doi:10.1016/j.xgen.2023.100361

Cited by 43 publications

(19 citation statements)

References 75 publications

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“…Natural selection and other demographic processes can result in regions of LRLD in the genome. In previous work, to facilitate genotype PCA analysis of the CKB cohort, we identified such regions of LRLD using an approach similar to one previously used in UKB (21), by applying an iterative hidden Markov-model based algorithm to principal components (PCs) derived from genotypes of 76,719 unrelated CKB individuals (see Methods ) (22). Excluding the extended region of LD at the chromosome 6 HLA region (chr6:20-40Mbp), we identified 229 unique regions of LRLD (median length = 593.1Kbp, total length = 218.1Mbp) on the basis of distortions in the variant loadings of the top 11 PCs (i.e.…”

Section: Resultsmentioning

confidence: 99%

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Natural selection exerted by historical coronavirus epidemic(s): comparative genetic analysis in China Kadoorie Biobank and UK Biobank

Morris,

Lin,

Millwood

et al. 2024

Preprint

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BackgroundPathogens have been one of the primary sources of natural selection affecting modern humans. The footprints of historical selection events – “selective sweeps” – can be detected in the genomes of present-day individuals. Previous analyses of 629 samples from the 1000 Genomes Project suggested that an ancient coronavirus epidemic ∼20,000 years ago drove multiple selective sweeps in the ancestors of present-day East Asians, but not in other worldwide populations.ResultsUsing a much larger genetic dataset of 76,719 unrelated individuals from each of the China Kadoorie Biobank (CKB) and UK Biobank (UKB) to identify regions of long-range linkage disequilibrium, we further investigated signatures of past selective sweeps and how they reflect previous viral epidemics. Using independently-curated lists of human host proteins which interact physically or functionally with viruses (virus-interacting proteins; VIPs), we found enrichment in CKB for regions of long-range linkage disequilibrium at genes encoding VIPs for coronaviruses, but not DNA viruses. By contrast, we found no clear evidence for any VIP enrichment in UKB. These findings were supported by additional analyses using saltiLASSi, a selection-scan method robust to false positives caused by demographic events. By contrast, for GWAS signals for SARS-Cov2 susceptibility (critical illness, hospitalisation, and reported infection), there was no difference between UKB and CKB in the number located at or near signals of selection, as expected for a novel virus which has had no opportunity to impact the CKB/UKB study populations.ConclusionsTogether, these results provide evidence of selection events consistent with historical coronavirus epidemic(s) originating in East Asia. These results show how biobank-scale datasets and evolutionary genomics theory can provide insight into the study of past epidemics. The results also highlights how historic infectious diseases epidemics can shape the genetic architecture of present-day human populations.

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Section: Resultsmentioning

confidence: 99%

“…The saltiLASSi (v-1.1.1) (15) algorithm was applied to the same CKB and UKB datasets of 76,719 participants each. After initial QC (22) no allele frequency/count filters were applied to the genotype data before applying the selection scan. We used the settings --winsize 10 and --winstep 1, with all other parameters as default.…”

Section: Methodsmentioning

confidence: 99%

Natural selection exerted by historical coronavirus epidemic(s): comparative genetic analysis in China Kadoorie Biobank and UK Biobank

Morris,

Lin,

Millwood

et al. 2024

Preprint

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“…Cox proportional hazards regression models were stratified for age-at-risk and ten areas, and adjusted for genomic principal components (PCs). 22 Log HRs were plotted against mean alcohol intake in each genotype-predicted alcohol intake category. To estimate the HR per 280 g/week, analyses were performed separately within each area with adjustment for age-at-risk and regional PCs.…”

Section: Methodsmentioning

confidence: 99%

Alcohol intake and cause-specific mortality: conventional and genetic evidence in a prospective cohort study of 512 000 adults in China

Millwood,

Im,

Bennett

et al. 2023

The Lancet Public Health

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“…The baseline survey, conducted from 2004 to 2008, covered 10 specific regions and included questionnaire data, physical measurements, and blood samples. In 2013–2014, a second survey was conducted with 25,091 participants aged 30–79 years, followed by a third survey in 2020–2021 with 25,087 participants ( 3 ). Importantly, a substantial cohort of over 22,000 individuals participated in at least two follow-ups, forming a crucial basis for future longitudinal analyses.…”

Section: Active Follow-up Cohortsmentioning

confidence: 99%