Citations 2
The protective gene dose effect of the APOEε2 allele on gray matter volume in cognitively unimpaired individuals
Salvadó, Gemma , Ferreira, Daniel , Operto, Grégory , Cumplido‐Mayoral, Irene , Falcón, Carles , Vilor‐Tejedor, Natàlia , Minguillón, Carolina , Groot, Colin , Barkhof, Frederik , Scheltens, Philip , Ossenkoppele, Rik , Kern, Silke , Zettergren, Anna , Hort, Jakub , Stomrud, Erik , Westen, Danielle van , Hansson, Oskar , Westman, Eric , Gispert, Juan Domingo , ADNI, ALFA study†, BioFINDER,, Crous‐Bou, Marta , Arenaza-Urquijo, Eider M , Cacciaglia, Raffaele , Falcon, Carles , Vilor-Tejedor, Natàlia , Minguillon, Carolina , Groot, Colin , van der Flier, Wiesje M , Barkhof, Frederik , Scheltens, Philip , Ossenkoppele, Rik , Skoog, Ingmar , Stomrud, Erik , van Westen, Danielle , Hansson, Oskar , Molinuevo, José Luis , Wahlund, Lars-Olof , Westman, Eric , Gispert, Juan Domingo , Ferreira, Daniel , Hort, Jakub , Arenaza‐Urquijo, Eider M. , Flier, Wiesje M. van der , Skoog, Ingmar , Molinuevo, José Luís , Wahlund, Lars‐Olof , ADNI, ALFA study†, BioFINDER,
Alzheimer's & Dementia | December 8, 2021 | Volume: 18 | Issue: 7 | Pages: 1383-1395
AbstractIntroductionHarboring two copies of the apolipoprotein E (APOE) ε2 allele strongly protects against Alzheimer's disease (AD). However, the effect of this genotype on gray matter (GM) volume in cognitively unimpaired individuals has not yet been described.MethodsMulticenter brain magnetic resonance images (MRIs) from cognitively unimpaired ε2 homozygotes were matched (1:1) against all other APOE genotypes for relevant confounders (n = 223). GM volumes of ε2 genotypic groups were compared to each other and to the reference group (APOE ε3/ε3).ResultsCarrying at least one ε2 allele was associated with larger GM volumes in brain areas typically affected by AD and also in areas associated with cognitive resilience. APOE ε2 homozygotes, but not APOE ε2 heterozygotes, showed larger GM volumes in areas related to successful aging.DiscussionIn addition to the known resistance against amyloid‐β deposition, the larger GM volumes in key brain regions may confer APOE ε2 homozygotes additional protection against AD‐related cognitive decline.
Mendelian randomization analyses suggest a role for cholesterol in the development of endometrial cancer
Annibali, Daniela , Ashton, Katie A. , Auer, Paul L. , Beckmann, Matthias W. , Black, Amanda , Brinton, Louise A. , Buchanan, Daniel D. , Chen, Chu , Chen, Maxine , Cheng, Timothy, Crous‐Bou, Marta , Vivo, Immaculata De , Dörk, Thilo , Dowdy, Sean C. , Easton, Douglas F. , Ekici, Arif B. , Fasching, Peter A. , García‐Closas, Montserrat , Gaudet, Mia M. , Goode, Ellen L. , Gorman, Maggie, Haiman, Christopher A. , Hankinson, Susan E. , Hein, Alexander , Hillemanns, Peter , Hodgson, Shirley, Høivik, Erling A. , Holliday, Elizabeth , Hunter, David J., Lambrechts, Diether , Liang, Xiaolin , Lindblom, Annika , Lissowska, Jolanta , Magliocco, Anthony M., Martin, Lynn , McEvoy, Mark , Mints, Miriam, Nassir, Rami , Otton, Geoffrey, Palles, Claire , Pooler, Loreall , Proietto, Tony, Rübner, Matthias, Runnebaum, Ingo B. , Sacerdote, Carlotta , Sarto, Gloria E., Scott, Rodney J. , Shah, Mitul , Sheng, Xin , Tomlinson, Ian , Trovik, Jone , Wang, Zhaoming , Wentzensen, Nicolas , Xia, Lucy , Webb, Penelope M. , Thompson, Deborah J. , Glubb, Dylan M., O’Mara, Tracy A. , Lambrechts, Diether , Buchanan, Daniel D , Chen, Chu , De Vivo, Immaculata , Dörk, Thilo , Fasching, Peter A , Friedenreich, Christine M , Gaudet, Mia M , Goode, Ellen L , Lu, Lingeng , Sacerdote, Carlotta , Shu, Xiao-Ou , Wang, Zhaoming , Wentzensen, Nicolas , Xiang, Yong‐Bing , Yu, Herbert , Spurdle, Amanda B , O'Mara, Tracy A , Lambrechts, Diether , Webb, Penelope M , Hein, Alexander , Hillemanns, Peter , Lissowska, Jolanta , Lambrechts, Diether , García-Closas, Montserrat , Ekici, Arif B , Nassir, Rami , Palles, Claire , Lindblom, Annika , Kho, Pik Fang , Amant, Frédéric , Attia, John , Chanock, Stephen Jacob , Cook, Linda S. , Czene, Kamila , Dennis, Joe , Dunning, Alison M. , Dürst, Matthias , Fridley, Brooke L. , Giles, Graham G. , Hall, Per N , Hankinson, Susan E. , Jones, Angela, Kraft, Peter , Krakstad, Camilla , Marchand, Loı̈c Le , Long, Jirong , Milne, Roger L. , Mints, Miriam , Rebbeck, Timothy R. , Renner, Stefan P. , Risch, Harvey A. , Schumacher, Fredrick R. , Setiawan, Veronica Wendy , Shu, Xiao‐Ou , Southey, Melissa C. , Tham, Emma , Turman, Constance , Tyrer, Jonathan P. , Berg, David Van Den , Yang, Hannah , Yu, Kai , Zheng, Wei , Spurdle, Amanda B.
International Journal of Cancer | July 13, 2020 | Volume: 148 | Issue: 2 | Pages: 307-319
Abstract Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low‐density lipoprotein [LDL] and high‐density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels ( P < 5 × 10 −8 ) were identified as instrumental variables, and assessed using genome‐wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non‐endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non‐endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non‐endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non‐endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.