title: Genome-wide association study of age at menarche in African-American women.
abstract: African-American (AA) women have earlier menarche on average than women of European ancestry (EA), and earlier menarche is a risk factor for obesity and type 2 diabetes among other chronic diseases. Identification of common genetic variants associated with age at menarche has a potential value in pointing to the genetic pathways underlying chronic disease risk, yet comprehensive genome-wide studies of age at menarche are lacking for AA women. In this study, we tested the genome-wide association of self-reported age at menarche with common single-nucleotide polymorphisms (SNPs) in a total of 18 089 AA women in 15 studies using an additive genetic linear regression model, adjusting for year of birth and population stratification, followed by inverse-variance weighted meta-analysis (Stage 1). Top meta-analysis results were then tested in an independent sample of 2850 women (Stage 2). First, while no SNP passed the pre-specified P < 5 × 10(-8) threshold for significance in Stage 1, suggestive associations were found for variants near FLRT2 and PIK3R1, and conditional analysis identified two independent SNPs (rs339978 and rs980000) in or near RORA, strengthening the support for this suggestive locus identified in EA women. Secondly, an investigation of SNPs in 42 previously identified menarche loci in EA women demonstrated that 25 (60%) of them contained variants significantly associated with menarche in AA women. The findings provide the first evidence of cross-ethnic generalization of menarche loci identified to date, and suggest a number of novel biological links to menarche timing in AA women.
authors.affiliation: Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. ewd@umn.edu
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Demerath
authors.forename: Ching-Ti
authors.initials: CT
authors.lastname: Liu
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Gary
authors.initials: G
authors.lastname: Chen
authors.forename: Julie R
authors.initials: JR
authors.lastname: Palmer
authors.forename: Erin N
authors.initials: EN
authors.lastname: Smith
authors.forename: Christina T L
authors.initials: CT
authors.lastname: Chen
authors.forename: Christine B
authors.initials: CB
authors.lastname: Ambrosone
authors.forename: Alice M
authors.initials: AM
authors.lastname: Arnold
authors.forename: Elisa V
authors.initials: EV
authors.lastname: Bandera
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Berenson
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Angela
authors.initials: A
authors.lastname: Britton
authors.forename: Anne R
authors.initials: AR
authors.lastname: Cappola
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Deming
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Elks
authors.forename: Michelle K
authors.initials: MK
authors.lastname: Evans
authors.forename: Zofia
authors.initials: Z
authors.lastname: Gajdos
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hu
authors.forename: Sue
authors.initials: S
authors.lastname: Ingles
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Lu
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Solomon K
authors.initials: SK
authors.lastname: Musani
authors.forename: Nora L
authors.initials: NL
authors.lastname: Nock
authors.forename: Kari
authors.initials: K
authors.lastname: North
authors.forename: Sarah
authors.initials: S
authors.lastname: Nyante
authors.forename: Michael F
authors.initials: MF
authors.lastname: Press
authors.forename: Jorge L
authors.initials: JL
authors.lastname: Rodriquez-Gil
authors.forename: Edward A
authors.initials: EA
authors.lastname: Ruiz-Narvaez
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Sathanur R
authors.initials: SR
authors.lastname: Srinivasan
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Woods
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Regina G
authors.initials: RG
authors.lastname: Ziegler
authors.forename: Alan
authors.initials: A
authors.lastname: Zonderman
authors.forename: Gerardo
authors.initials: G
authors.lastname: Heiss
authors.forename: B
authors.initials: B
authors.lastname: Gwen Windham
authors.forename: Melissa
authors.initials: M
authors.lastname: Wellons
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Murray
authors.forename: Michael
authors.initials: M
authors.lastname: Nalls
authors.forename: Tomi
authors.initials: T
authors.lastname: Pastinen
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Rajkovic
authors.forename: Joel
authors.initials: J
authors.lastname: Hirschhorn
authors.forename: L
authors.initials: L
authors.lastname: Adrienne Cupples
authors.forename: Charles
authors.initials: C
authors.lastname: Kooperberg
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
mesh_terms: D000293:Adolescent; D001741:Black or African American / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D005260:Female; D056426:Genetic Loci; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics; D008572:Menarche / Q000235:genetics*; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C404491:FLRT2 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human