Dataset Information

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

ABSTRACT: Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P?

SUBMITTER: Perry JR

PROVIDER: S-EPMC4185210 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Perry John Rb JR Day Felix F Elks Cathy E CE Sulem Patrick P Thompson Deborah J DJ Ferreira Teresa T He Chunyan C Chasman Daniel I DI Esko Tõnu T Thorleifsson Gudmar G Albrecht Eva E Ang Wei Q WQ Corre Tanguy T Cousminer Diana L DL Feenstra Bjarke B Franceschini Nora N Ganna Andrea A Johnson Andrew D AD Kjellqvist Sanela S Lunetta Kathryn L KL McMahon George G Nolte Ilja M IM Paternoster Lavinia L Porcu Eleonora E Smith Albert V AV Stolk Lisette L Teumer Alexander A Tšernikova Natalia N Tikkanen Emmi E Ulivi Sheila S Wagner Erin K EK Amin Najaf N Bierut Laura J LJ Byrne Enda M EM Hottenga Jouke-Jan JJ Koller Daniel L DL Mangino Massimo M Pers Tune H TH Yerges-Armstrong Laura M LM Zhao Jing Hua JH Andrulis Irene L IL Anton-Culver Hoda H Atsma Femke F Bandinelli Stefania S Beckmann Matthias W MW Benitez Javier J Blomqvist Carl C Bojesen Stig E SE Bolla Manjeet K MK Bonanni Bernardo B Brauch Hiltrud H Brenner Hermann H Buring Julie E JE Chang-Claude Jenny J Chanock Stephen S Chen Jinhui J Chenevix-Trench Georgia G Collée J Margriet JM Couch Fergus J FJ Couper David D Coveillo Andrea D AD Cox Angela A Czene Kamila K D'adamo Adamo Pio AP Smith George Davey GD De Vivo Immaculata I Demerath Ellen W EW Dennis Joe J Devilee Peter P Dieffenbach Aida K AK Dunning Alison M AM Eiriksdottir Gudny G Eriksson Johan G JG Fasching Peter A PA Ferrucci Luigi L Flesch-Janys Dieter D Flyger Henrik H Foroud Tatiana T Franke Lude L Garcia Melissa E ME García-Closas Montserrat M Geller Frank F de Geus Eco Ej EE Giles Graham G GG Gudbjartsson Daniel F DF Gudnason Vilmundur V Guénel Pascal P Guo Suiqun S Hall Per P Hamann Ute U Haring Robin R Hartman Catharina A CA Heath Andrew C AC Hofman Albert A Hooning Maartje J MJ Hopper John L JL Hu Frank B FB Hunter David J DJ Karasik David D Kiel Douglas P DP Knight Julia A JA Kosma Veli-Matti VM Kutalik Zoltan Z Lai Sandra S Lambrechts Diether D Lindblom Annika A Mägi Reedik R Magnusson Patrik K PK Mannermaa Arto A Martin Nicholas G NG Masson Gisli G McArdle Patrick F PF McArdle Wendy L WL Melbye Mads M Michailidou Kyriaki K Mihailov Evelin E Milani Lili L Milne Roger L RL Nevanlinna Heli H Neven Patrick P Nohr Ellen A EA Oldehinkel Albertine J AJ Oostra Ben A BA Palotie Aarno A Peacock Munro M Pedersen Nancy L NL Peterlongo Paolo P Peto Julian J Pharoah Paul Dp PD Postma Dirkje S DS Pouta Anneli A Pylkäs Katri K Radice Paolo P Ring Susan S Rivadeneira Fernando F Robino Antonietta A Rose Lynda M LM Rudolph Anja A Salomaa Veikko V Sanna Serena S Schlessinger David D Schmidt Marjanka K MK Southey Mellissa C MC Sovio Ulla U Stampfer Meir J MJ Stöckl Doris D Storniolo Anna M AM Timpson Nicholas J NJ Tyrer Jonathan J Visser Jenny A JA Vollenweider Peter P Völzke Henry H Waeber Gerard G Waldenberger Melanie M Wallaschofski Henri H Wang Qin Q Willemsen Gonneke G Winqvist Robert R Wolffenbuttel Bruce Hr BH Wright Margaret J MJ Boomsma Dorret I DI Econs Michael J MJ Khaw Kay-Tee KT Loos Ruth Jf RJ McCarthy Mark I MI Montgomery Grant W GW Rice John P JP Streeten Elizabeth A EA Thorsteinsdottir Unnur U van Duijn Cornelia M CM Alizadeh Behrooz Z BZ Bergmann Sven S Boerwinkle Eric E Boyd Heather A HA Crisponi Laura L Gasparini Paolo P Gieger Christian C Harris Tamara B TB Ingelsson Erik E Järvelin Marjo-Riitta MR Kraft Peter P Lawlor Debbie D Metspalu Andres A Pennell Craig E CE Ridker Paul M PM Snieder Harold H Sørensen Thorkild Ia TI Spector Tim D TD Strachan David P DP Uitterlinden André G AG Wareham Nicholas J NJ Widen Elisabeth E Zygmunt Marek M Murray Anna A Easton Douglas F DF Stefansson Kari K Murabito Joanne M JM Ong Ken K KK

Nature 20140723 7520

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and c ...[more]

PMID: 25231870

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Project description:BACKGROUND:Genomic imprinting, mediated by parent-of-origin-specific epigenetic silencing, adjusts the gene expression dosage in mammals. We aimed to clarify parental allelic expression in the human placenta for 396 claimed candidate imprinted genes and to assess the evidence for the proposed enrichment of imprinted expression in the placenta. The study utilized RNA-Seq-based transcriptome and genotyping data from 54 parental-placental samples representing the three trimesters of gestation, and term cases of preeclampsia, gestational diabetes, and fetal growth disturbances. RESULTS:Almost half of the targeted genes (n = 179; 45%) were either not transcribed or showed limited expression in the human placenta. After filtering for the presence of common exonic SNPs, adequacy of sequencing reads and informative families, 91 genes were retained (43 loci form Geneimprint database; 48 recently proposed genes). Only 11/91 genes (12.1%) showed confident signals of imprinting (binomial test, Bonferroni corrected P < 0.05; > 90% transcripts originating from one parental allele). The confirmed imprinted genes exhibit enriched placental expression (PHLDA2, H19, IGF2, MEST, ZFAT, PLAGL1, AIM1) or are transcribed additionally only in the adrenal gland (MEG3, RTL1, PEG10, DLK1). Parental monoallelic expression showed extreme stability across gestation and in term pregnancy complications. A distinct group of additional 14 genes exhibited a statistically significant bias in parental allelic proportions defined as having 65-90% of reads from one parental allele (e.g., KLHDC10, NLRP2, RHOBTB3, DNMT1). Molecular mechanisms behind biased parental expression are still to be clarified. However, 66 of 91 (72.5%) analyzed candidate imprinted genes showed no signals of deviation from biallelic expression. CONCLUSIONS:As placental tissue is not included in The Genotype-Tissue Expression (GTEx) project, the study contributed to fill the gap in the knowledge concerning parental allelic expression. A catalog of parental allelic proportions and gene expression of analyzed loci across human gestation and in term pregnancy complications is provided as additional files. The study outcome suggested that true imprinting in the human placenta is restricted to well-characterized loci. High expression of imprinted genes during mid-pregnancy supports their critical role in developmental programming. Consistent with the data on other GTEx tissues, the number of human imprinted genes appears to be overestimated.

Dataset Information

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Publications

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

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