Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk
Felix R. Day,Deborah J. Thompson,Hannes Helgason,Hannes Helgason,Daniel I. Chasman,Hilary K. Finucane,Hilary K. Finucane,Patrick Sulem,Katherine S. Ruth,Sean Whalen,Abhishek Sarkar,Abhishek Sarkar,Eva Albrecht,Elisabeth Altmaier,Marzyeh Amini,Caterina Barbieri,Thibaud Boutin,Archie Campbell,Ellen W. Demerath,Ayush Giri,Chunyan He,Jouke J. Hottenga,Robert Karlsson,Ivana Kolcic,Po-Ru Loh,Po-Ru Loh,Kathryn L. Lunetta,Kathryn L. Lunetta,Massimo Mangino,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,Sven Bergmann,Murielle Bochud,Eric Boerwinkle,Stig E. Bojesen,Manjeet K. Bolla,Judith S. Brand,Hiltrud Brauch,Hiltrud Brauch,Hiltrud Brauch,Hermann Brenner,Linda Broer,Thomas Brüning,Julie E. Buring,Harry Campbell,Eulalia Catamo,Stephen J. Chanock,Georgia Chenevix-Trench,Tanguy Corre,Tanguy Corre,Fergus J. Couch,Diana L. Cousminer,Angela Cox,Laura Crisponi,Kamila Czene,George Davey Smith,Eco J. C. 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,Peter A. Fasching,Lindsay Fernández-Rhodes,Luigi Ferrucci,Dieter Flesch-Janys,Lude Franke,Marike Gabrielson,Ilaria Gandin,Graham G. Giles,Graham G. Giles,Harald Grallert,Daniel F. Gudbjartsson,Daniel F. Gudbjartsson,Pascal Guénel,Per Hall,Emily Hallberg,Ute Hamann,Tamara B. Harris,Catharina A. Hartman,Gerardo Heiss,Maartje J. Hooning,John L. Hopper,Frank B. Hu,David J. Hunter,M. Arfan Ikram,Hae Kyung Im,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Peter K. Joshi,David Karasik,Manolis Kellis,Manolis Kellis,Zoltán Kutalik,Zoltán Kutalik,Genevieve Lachance,Diether Lambrechts,Claudia Langenberg,Lenore J. Launer,Joop S.E. Laven,Stefania Lenarduzzi,Jingmei Li,Penelope A. Lind,Sara Lindström,Yongmei Liu,Jian'an Luan,Reedik Mägi,Arto Mannermaa,Hamdi Mbarek,Mark I. McCarthy,Christa Meisinger,Thomas Meitinger,Cristina Menni,Andres Metspalu,Kyriaki Michailidou,Kyriaki Michailidou,Lili Milani,Roger L. Milne,Roger L. Milne,Grant W. Montgomery,Anna Marie Mulligan,Mike A. Nalls,Pau Navarro,Heli Nevanlinna,Dale R. Nyholt,Albertine J. Oldehinkel,Tracy A. O'Mara,Sandosh Padmanabhan,Aarno Palotie,Nancy L. Pedersen,Annette Peters,Julian Peto,Paul D.P. Pharoah,Anneli Pouta,Paolo Radice,Iffat Rahman,Susan M. Ring,Antonietta Robino,Frits R. Rosendaal,Igor Rudan,Rico Rueedi,Rico Rueedi,Daniela Ruggiero,Cinzia Sala,Marjanka K. Schmidt,Robert A. Scott,Mitul Shah,Rossella Sorice,Melissa C. Southey,Ulla Sovio,Ulla Sovio,Meir J. Stampfer,Maristella Steri,Konstantin Strauch,Toshiko Tanaka,Emmi Tikkanen,Nicholas J. Timpson,Michela Traglia,Thérèse Truong,Jonathan Tyrer,André G. Uitterlinden,Digna R. Velez Edwards,Veronique Vitart,Uwe Völker,Peter Vollenweider,Qin Wang,Elisabeth Widen,Ko Willems van Dijk,Gonneke Willemsen,Robert Winqvist,Bruce H. R. Wolffenbuttel,Jing Hua Zhao,Magdalena Zoledziewska,Marek Zygmunt,Behrooz Z. Alizadeh,Dorret I. Boomsma,Marina Ciullo,Francesco Cucca,Tõnu Esko,Tõnu Esko,Nora Franceschini,Christian Gieger,Vilmundur Gudnason,Caroline Hayward,Peter Kraft,Debbie A Lawlor,Patrik K. E. Magnusson,Nicholas G. Martin,Dennis O. Mook-Kanamori,Ellen A. Nohr,Ozren Polasek,David J. Porteous,Alkes L. Price,Alkes L. Price,Alkes L. Price,Paul M. Ridker,Harold Snieder,Tim D. Spector,Doris Stöckl,Daniela Toniolo,Sheila Ulivi,Jenny A. Visser,Henry Völzke,Nicholas J. Wareham,James F. Wilson,Amanda B. Spurdle,Unnur Thorsteindottir,Unnur Thorsteindottir,Katherine S. Pollard,Katherine S. Pollard,Douglas F. Easton,Joyce Y. Tung,Jenny Chang-Claude,Jenny Chang-Claude,David A. Hinds,Anna Murray,Joanne M. Murabito,Joanne M. Murabito,Kari Stefansson,Kari Stefansson,Ken K. Ong,John R. B. Perry +244 more
TLDR
In this article, the authors used 1000 Genomes Project-imputed genotype data in up to ∼370,000 women to identify 389 independent signals (P < 5 × 10-8) for age at menarche, a milestone in female pubertal development.Abstract:
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 (P < 5 × 10-8) 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 (BMI), 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.read more
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Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Jason Ernst,Angela Yen,Pouya Kheradpour,Zhizhuo Zhang,Jianrong Wang,Lucas D. Ward,Abhishek Sarkar,Gerald Quon,Matthew L. Eaton,Yi-Chieh Wu,Andreas R. Pfenning,Xinchen Wang,Melina Claussnitzer,Yaping Liu,Mukul S. Bansal,Soheil Feizi-Khankandi,Ah Ram Kim,Richard C Sallari,Nicholas A Sinnott-Armstrong,Laurie A. Boyer,Elizabeta Gjoneska,Li-Huei Tsai,Manolis Kellis +24 more
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
The Lin28/let-7 Axis Regulates Glucose Metabolism
Hao Zhu,Ng Shyh-Chang,Ayellet V. Segrè,Ayellet V. Segrè,Gen Shinoda,Samar P. Shah,William S. Einhorn,William S. Einhorn,Ayumu Takeuchi,Jesse M. Engreitz,John P. Hagan,Michael G. Kharas,Michael G. Kharas,Achia Urbach,James E. Thornton,Robinson Triboulet,Richard I. Gregory,David Altshuler,David Altshuler,George Q. Daley +19 more
TL;DR: The Lin28/let-7 pathway is established as a central regulator of mammalian glucose metabolism and enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies.
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Clinical Management of Congenital Hypogonadotropic Hypogonadism
Jacques Young,Jacques Young,Cheng Xu,Georgios Papadakis,James S Acierno,Luigi Maione,Luigi Maione,Johanna Hietamäki,Taneli Raivio,Nelly Pitteloud +9 more
TL;DR: This review is a comprehensive synthesis of the current literature available regarding the diagnosis, patient management, and genetic foundations of CHH relative to normal reproductive development.
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Sex-dependent dominance maintains migration supergene in rainbow trout
Devon E. Pearse,Nicola J. Barson,Torfinn Nome,Guangtu Gao,Matthew A. Campbell,Alicia Abadía-Cardoso,Eric C. Anderson,David E. Rundio,Thomas N. Williams,Kerry A. Naish,Thomas Moen,Sixin Liu,Matthew Peter Kent,Michel Moser,David R. Minkley,Eric Rondeau,Marine S. O. Brieuc,Simen Rød Sandve,Michael R. Miller,Lucydalila Cedillo,Kobi Baruch,Alvaro G. Hernandez,Gil Ben-Zvi,Doron Shem-Tov,Omer Barad,K. V. Kuzishchin,John Carlos Garza,Steven T. Lindley,Ben F. Koop,Gary H. Thorgaard,Yniv Palti,Sigbjørn Lien +31 more
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Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits.
Farhad Hormozdiari,Farhad Hormozdiari,Steven Gazal,Steven Gazal,Bryce van de Geijn,Bryce van de Geijn,Hilary K. Finucane,Hilary K. Finucane,Chelsea J.-T. Ju,Po-Ru Loh,Po-Ru Loh,Armin P. Schoech,Armin P. Schoech,Yakir A. Reshef,Yakir A. Reshef,Xuanyao Liu,Xuanyao Liu,Luke J. O’Connor,Alexander Gusev,Alexander Gusev,Eleazar Eskin,Alkes L. Price,Alkes L. Price +22 more
TL;DR: A new set of functional annotations based on fine-mapped molecular quantitative trait loci from GTEx and BLUEPRINT consortium data are enriched for disease heritability across 41 diseases and complex traits.
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