Cuellar-Partida, G;
Lu, Y;
Dixon, SC;
Fasching, PA;
Hein, A;
Burghaus, S;
Beckmann, MW;
... MacGregor, S; + view all
(2016)
Assessing the genetic architecture of epithelial ovarian cancer histological subtypes.
Human Genetics
, 135
(7)
pp. 741-756.
10.1007/s00439-016-1663-9.
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Abstract
Epithelial ovarian cancer (EOC) is one of the deadliest common cancers. The five most common types of disease are high-grade and low-grade serous, endometrioid, mucinous and clear cell carcinoma. Each of these subtypes present distinct molecular pathogeneses and sensitivities to treatments. Recent studies show that certain genetic variants confer susceptibility to all subtypes while other variants are subtype-specific. Here, we perform an extensive analysis of the genetic architecture of EOC subtypes. To this end, we used data of 10,014 invasive EOC patients and 21,233 controls from the Ovarian Cancer Association Consortium genotyped in the iCOGS array (211,155 SNPs). We estimate the array heritability (attributable to variants tagged on arrays) of each subtype and their genetic correlations. We also look for genetic overlaps with factors such as obesity, smoking behaviors, diabetes, age at menarche and height. We estimated the array heritabilities of high-grade serous disease (h2g = 8.8 ± 1.1 %), endometrioid (h2g = 3.2 ± 1.6 %), clear cell (h2g = 6.7 ± 3.3 %) and all EOC (h2g = 5.6 ± 0.6 %). Known associated loci contributed approximately 40 % of the total array heritability for each subtype. The contribution of each chromosome to the total heritability was not proportional to chromosome size. Through bivariate and cross-trait LD score regression, we found evidence of shared genetic backgrounds between the three high-grade subtypes: serous, endometrioid and undifferentiated. Finally, we found significant genetic correlations of all EOC with diabetes and obesity using a polygenic prediction approach.
| Type: | Article |
|---|---|
| Title: | Assessing the genetic architecture of epithelial ovarian cancer histological subtypes |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00439-016-1663-9 |
| Publisher version: | http://dx.doi.org/10.1007/s00439-016-1663-9 |
| Language: | English |
| Additional information: | Copyright © Springer-Verlag Berlin Heidelberg 2016. The final publication is available at Springer via http://dx.doi.org/10.1007/s00439-016-1663-9 |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, GENOME-WIDE ASSOCIATION, MOLECULAR CHARACTERIZATION, SUSCEPTIBILITY LOCUS, DIABETES-MELLITUS, PROVIDES INSIGHTS, HUMAN HEIGHT, COMMON SNPS, RISK, METAANALYSIS, MUTATIONS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology > MRC Clinical Trials Unit at UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1483125 |
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