Caterina Barbieri: Publications

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Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk
with Felix R. Day, Deborah J. Thompson, Hannes Helgason, Daniel I. Chasman, Hilary Finucane, Patrick Sulem, Katherine S. Ruth, Sean Whalen, Abhishek K. Sarkar, Eva Albrecht, Elisabeth Altmaier, Marzyeh Amini, Thibaud Boutin, Archie Campbell, Ellen Demerath, Ayush Giri, Chunyan He, Jouke J. Hottenga, Robert Karlsson, Ivana Kolcic, Po-Ru Loh, Kathryn L. Lunetta, Massimo Mangino, Brumat Marco, George McMahon, Sarah E. Medland, Ilja M. Nolte, Raymond Noordam, Teresa Nutile, Lavinia Paternoster, Natalia Perjakova, Eleonora Porcu, Lynda M. Rose, Katharina E. Schraut, Ayellet V. Segrè, Albert V. Smith, Lisette Stolk, Alexander Teumer, Irene L. Andrulis, Stefania Bandinelli, Matthias W. Beckmann, Javier Benitez, Sven Bergmann, Murielle Bochud, Eric Boerwinkle, Stig E. Bojesen, Manjeet K. Bolla, Judith S. Brand, Hiltrud Brauch, Hermann Brenner, Linda Broer, Thomas Brüning, Julie E. Buring, Harry Campbell, Eulalia Catamo, Stephen Chanock, Georgia Chenevix-Trench, Tanguy Corre, Fergus J. Couch, Diana L. Cousminer, Angela Cox, Laura Crisponi, Kamila Czene, George Davey Smith, Eco J. C. N. de Geus, Renée de Mutsert, Immaculata De Vivo, Joe Dennis, Peter Devilee, Isabel dos-Santos-Silva, Alison M. Dunning, Johan G. Eriksson, Peter A. Fasching, Lindsay Fernández-Rhodes, Luigi Ferrucci, Dieter Flesch-Janys, Lude Franke, Marike Gabrielson, Ilaria Gandin, Graham G. Giles, Harald Grallert, Daniel F. Gudbjartsson, Pascal Guénel, and Per Hall

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or asso…Read more
The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index, between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.