| Title | Rare coding variants and X-linked loci associated with age at menarche. |
| Publication Type | Journal Article |
| Year of Publication | 2015 |
| Authors | Lunetta KL, Day FR, Sulem P, Ruth KS, Tung JY, Hinds DA, Esko T, Elks CE, Altmaier E, He C, Huffman JE, Mihailov E, Porcu E, Robino A, Rose LM, Schick UM, Stolk L, Teumer A, Thompson DJ, Traglia M, Wang CA, Yerges-Armstrong LM, Antoniou AC, Barbieri C, Coviello AD, Cucca F, Demerath EW, Dunning AM, Gandin I, Grove ML, Gudbjartsson DF, Hocking LJ, Hofman A, Huang J, Jackson RD, Karasik D, Kriebel J, Lange EM, Lange LA, Langenberg C, Li X, Luan J'an, Mägi R, Morrison AC, Padmanabhan S, Pirie A, Polasek O, Porteous D, Reiner AP, Rivadeneira F, Rudan I, Sala CF, Schlessinger D, Scott RA, Stöckl D, Visser JA, Völker U, Vozzi D, Wilson JG, Zygmunt M, Boerwinkle E, Buring JE, Crisponi L, Easton DF, Hayward C, Hu FB, Liu S, Metspalu A, Pennell CE, Ridker PM, Strauch K, Streeten EA, Toniolo D, Uitterlinden AG, Ulivi S, Völzke H, Wareham NJ, Wellons M, Franceschini N, Chasman DI, Thorsteinsdottir U, Murray A, Stefansson K, Murabito JM, Ong KK |
| Secondary Authors | Perry JRB |
| Corporate Authors | EPIC-InterAct Consortium, Generation Scotland |
| Journal | Nat Commun |
| Volume | 6 |
| Pagination | 7756 |
| Date Published | 2015 Aug 04 |
| ISSN | 2041-1723 |
| Keywords | Adolescent, Adult, Age Factors, Aged, Amides, AMP-Activated Protein Kinases, Autoantigens, Cell Cycle Proteins, Chromosomes, Human, X, Codon, Nonsense, Energy Metabolism, European Continental Ancestry Group, Fatty Acids, Female, Gene Frequency, Genes, X-Linked, Genetic Variation, Genotype, Humans, Hypogonadism, Immunoglobulins, Laminin, Membrane Proteins, Menarche, Middle Aged, Mutation, Missense, Penetrance, Phenotype, Proteins, Receptors, Neurokinin-3, RNA Interference, RNA-Binding Proteins, Signal Transduction, Young Adult |
| Abstract | More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P |
| DOI | 10.1038/ncomms8756 |
| Alternate Journal | Nat Commun |
| PubMed ID | 26239645 |
| PubMed Central ID | PMC4538850 |
| Grant List | MC_UP_A100_1003 / / Medical Research Council / United Kingdom 11174 / / Cancer Research UK / United Kingdom P30 CA015704 / CA / NCI NIH HHS / United States MR/K026992/1 / / Medical Research Council / United Kingdom UL1 TR001108 / TR / NCATS NIH HHS / United States MC_UU_12015/1 / / Medical Research Council / United Kingdom MC_U106179471 / / Medical Research Council / United Kingdom MC_UU_12015/2 / / Medical Research Council / United Kingdom MC_U106179472 / / Medical Research Council / United Kingdom R01 AG029451 / AG / NIA NIH HHS / United States CZD/16/6/4 / / Chief Scientist Office / United Kingdom MC_PC_U127561128 / / Medical Research Council / United Kingdom UM1 CA182913 / CA / NCI NIH HHS / United States R21 AG032598 / AG / NIA NIH HHS / United States MC_UU_12015/5 / / Medical Research Council / United Kingdom |