Browsing by Author "Cornelis, Marilyn C."

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    A genome-wide association study of early menopause and the combined impact of identified variants
    (Oxford University Press, 2013) Perry, John R. B.; Corre, Tanguy; Esko, Tõnu; Chasman, Daniel I.; Fischer, Krista; Franceschini, Nora; He, Chunyan; Kutalik, Zoltan; Mangino, Massimo; Rose, Lynda M.; Smith, Albert Vernon; Stolk, Lisette; Sulem, Patrick; Weedon, Michael N.; Zhuang, Wei V.; Arnold, Alice; Ashworth, Alan; Bergmann, Sven; Buring, Julie E.; Burri, Andrea; Chen, Constance; Cornelis, Marilyn C.; Couper, David J.; Goodarzi, Mark O.; Gudnason, Vilmundur; Harris, Tamara; Hofman, Albert; Jones, Michael; Kraft, Peter; Launer, Lenore; Laven, Joop S. E.; Li, Guo; McKnight, Barbara; Masciullo, Corrado; Milani, Lili; Orr, Nicholas; Psaty, Bruce M.; ReproGen Consortium; Ridker, Paul M.; Rivadeneira, Fernando; Sala, Cinzia; Salumets, Andres; Schoemaker, Minouk; Traglia, Michela; Waeber, Gérard; Chanock, Stephen J.; Demerath, Ellen W.; Garcia, Melissa; Hankinson, Susan E.; Hu, Frank B.; Hunter, David J.; Lunetta, Kathryn L.; Metspalu, Andres; Montgomery, Grant W.; Murabito, Joanne M.; Newman, Anne B.; Ong, Ken K.; Spector, Tim D.; Stefansson, Kari; Swerdlow, Anthony J.; Thorsteinsdottir, Unnur; Van Dam, Rob M.; Uitterlinden, André G.; Visser, Jenny A.; Vollenweider, Peter; Toniolo, Daniela; Murray, Anna; Medicine, School of Medicine
    Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smoking.
  • Thumbnail Image
    Item
    A genome-wide analysis of gene–caffeine consumption interaction on basal cell carcinoma
    (Oxford University Press, 2016-12) Li, Xin; Cornelis, Marilyn C.; Liang, Liming; Song, Fengju; De Vivo, Immaculata; Giovannucci, Edward; Tang, Jean Y.; Han, Jiali; Epidemiology, School of Public Health
    p53 plays an important role in silibinin-mediated inhibition of UVB-induced skin carcinogenesis and associated inflammatory response in SKH-1 hairless mouse. Silibinin-mediated repair of UVB-induced DNA damage is only partially dependent on p53., Animal models have suggested that oral or topical administration of caffeine could inhibit ultraviolet-induced carcinogenesis via the ataxia telangiectasia and rad3 (ATR)-related apoptosis. Previous epidemiological studies have demonstrated that increased caffeine consumption is associated with reduced risk of basal cell carcinoma (BCC). To identify common genetic markers that may modify this association, we tested gene–caffeine intake interaction on BCC risk in a genome-wide analysis. We included 3383 BCC cases and 8528 controls of European ancestry from the Nurses’ Health Study and Health Professionals Follow-up Study. Single nucleotide polymorphism (SNP) rs142310826 near the NEIL3 gene showed a genome-wide significant interaction with caffeine consumption (P = 1.78 × 10–8 for interaction) on BCC risk. There was no gender difference for this interaction (P = 0.64 for heterogeneity). NEIL3, a gene belonging to the base excision DNA repair pathway, encodes a DNA glycosylase that recognizes and removes lesions produced by oxidative stress. In addition, we identified several loci with P value for interaction <5 × 10–7 in gender-specific analyses (P for heterogeneity between genders < 0.001) including those mapping to the genes LRRTM4, ATF3 and DCLRE1C in women and POTEA in men. Finally, we tested the associations between caffeine consumption-related SNPs reported by previous genome-wide association studies and risk of BCC, both individually and jointly, but found no significant association. In sum, we identified a DNA repair gene that could be involved in caffeine-mediated skin tumor inhibition. Further studies are warranted to confirm these findings.