dc.contributor.author | Malawsky, DS | |
dc.contributor.author | van Walree, E | |
dc.contributor.author | Jacobs, BM | |
dc.contributor.author | Heng, TH | |
dc.contributor.author | Huang, QQ | |
dc.contributor.author | Sabir, AH | |
dc.contributor.author | Rahman, S | |
dc.contributor.author | Sharif, SM | |
dc.contributor.author | Khan, A | |
dc.contributor.author | Mirkov, MU | |
dc.contributor.author | 23andMe Research Team | |
dc.contributor.author | Genes & Health Research Team | |
dc.contributor.author | Kuwahara, H | |
dc.contributor.author | Gao, X | |
dc.contributor.author | Alkuraya, FS | |
dc.contributor.author | Posthuma, D | |
dc.contributor.author | Newman, WG | |
dc.contributor.author | Griffiths, CJ | |
dc.contributor.author | Mathur, R | |
dc.contributor.author | van Heel, DA | |
dc.contributor.author | Finer, S | |
dc.contributor.author | O'Connell, J | |
dc.contributor.author | Martin, HC | |
dc.date.accessioned | 2023-10-19T12:32:32Z | |
dc.date.available | 2023-08-23 | |
dc.date.available | 2023-10-19T12:32:32Z | |
dc.date.issued | 2023-09-20 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/91435 | |
dc.description.abstract | Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (FROH) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of FROH. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between FROH and twelve common diseases. We replicated associations with type 2 diabetes (T2D) and post-traumatic stress disorder via within-sibling analysis in 23andMe (median n = 480,282). We estimated that autozygosity due to consanguinity accounts for 5%-18% of T2D cases among British Pakistanis. Our work highlights the possibility of widespread non-additive genetic effects on common diseases and has important implications for global populations with high rates of consanguinity. | en_US |
dc.language | eng | |
dc.relation.ispartof | Cell | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | autozygosity | en_US |
dc.subject | common diseases | en_US |
dc.subject | consanguinity | en_US |
dc.subject | diverse cohorts | en_US |
dc.subject | medical genetics | en_US |
dc.subject | recessive | en_US |
dc.title | Influence of autozygosity on common disease risk across the phenotypic spectrum. | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1016/j.cell.2023.08.028 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37757828 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
dcterms.dateAccepted | 2023-08-23 | |
qmul.funder | Phenotyping and Experimental Medicine Centre for naturally occurring Gene Knock-Outs in Humans::Medical Research Council | en_US |
qmul.funder | Phenotyping and Experimental Medicine Centre for naturally occurring Gene Knock-Outs in Humans::Medical Research Council | en_US |