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Rare coding variants and X-linked loci associated with age at menarche.

TitleRare coding variants and X-linked loci associated with age at menarche.
Publication TypeJournal Article
Year of Publication2015
AuthorsLunetta 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 AuthorsPerry JRB
Corporate AuthorsEPIC-InterAct Consortium, Generation Scotland
JournalNat Commun
Volume6
Pagination7756
Date Published2015 Aug 04
ISSN2041-1723
KeywordsAdolescent, 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

DOI10.1038/ncomms8756
Alternate JournalNat Commun
PubMed ID26239645
PubMed Central IDPMC4538850
Grant ListMC_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