title: Association of adiposity genetic variants with menarche timing in 92,105 women of European descent.
abstract: Obesity is of global health concern. There are well-described inverse relationships between female pubertal timing and obesity. Recent genome-wide association studies of age at menarche identified several obesity-related variants. Using data from the ReproGen Consortium, we employed meta-analytical techniques to estimate the associations of 95 a priori and recently identified obesity-related (body mass index (weight (kg)/height (m)(2)), waist circumference, and waist:hip ratio) single-nucleotide polymorphisms (SNPs) with age at menarche in 92,116 women of European descent from 38 studies (1970-2010), in order to estimate associations between genetic variants associated with central or overall adiposity and pubertal timing in girls. Investigators in each study performed a separate analysis of associations between the selected SNPs and age at menarche (ages 9-17 years) using linear regression models and adjusting for birth year, site (as appropriate), and population stratification. Heterogeneity of effect-measure estimates was investigated using meta-regression. Six novel associations of body mass index loci with age at menarche were identified, and 11 adiposity loci previously reported to be associated with age at menarche were confirmed, but none of the central adiposity variants individually showed significant associations. These findings suggest complex genetic relationships between menarche and overall obesity, and to a lesser extent central obesity, in normal processes of growth and development.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, 137 East Franklin Street, Suite 306, Campus Box 8050, Chapel Hill, NC 27514-8050, USA. fernandez-rhodes@unc.edu
authors.forename: Lindsay
authors.initials: L
authors.lastname: Fernández-Rhodes
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Demerath
authors.forename: Diana L
authors.initials: DL
authors.lastname: Cousminer
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.forename: Jill G
authors.initials: JG
authors.lastname: Dreyfus
authors.forename: Tõnu
authors.initials: T
authors.lastname: Esko
authors.forename: Albert V
authors.initials: AV
authors.lastname: Smith
authors.forename: Vilmundur
authors.initials: V
authors.lastname: Gudnason
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.forename: Lenore
authors.initials: L
authors.lastname: Launer
authors.forename: Patrick F
authors.initials: PF
authors.lastname: McArdle
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yerges-Armstrong
authors.forename: Cathy E
authors.initials: CE
authors.lastname: Elks
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kutalik
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Bjarke
authors.initials: B
authors.lastname: Feenstra
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boyd
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.forename: Evelin
authors.initials: E
authors.lastname: Mihailov
authors.forename: Linda
authors.initials: L
authors.lastname: Broer
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Ben
authors.initials: B
authors.lastname: Oostra
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Lunetta
authors.forename: John R B
authors.initials: JR
authors.lastname: Perry
authors.forename: Anna
authors.initials: A
authors.lastname: Murray
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.forename: Dongbing
authors.initials: D
authors.lastname: Lai
authors.forename: Tanguy
authors.initials: T
authors.lastname: Corre
authors.forename: Daniela
authors.initials: D
authors.lastname: Toniolo
authors.forename: Eva
authors.initials: E
authors.lastname: Albrecht
authors.forename: Doris
authors.initials: D
authors.lastname: Stöckl
authors.forename: Harald
authors.initials: H
authors.lastname: Grallert
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Chunyan
authors.initials: C
authors.lastname: He
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: David J
authors.initials: DJ
authors.lastname: Hunter
authors.forename: Jouke-Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Enda M
authors.initials: EM
authors.lastname: Byrne
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Warrington
authors.forename: Craig E
authors.initials: CE
authors.lastname: Pennell
authors.forename: Lisette
authors.initials: L
authors.lastname: Stolk
authors.forename: Jenny A
authors.initials: JA
authors.lastname: Visser
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Peng
authors.initials: P
authors.lastname: Lin
authors.forename: Sherri L
authors.initials: SL
authors.lastname: Fisher
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bierut
authors.forename: Laura
authors.initials: L
authors.lastname: Crisponi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Porcu
authors.forename: Massimo
authors.initials: M
authors.lastname: Mangino
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Julie E
authors.initials: JE
authors.lastname: Buring
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Rose
authors.forename: Paul M
authors.initials: PM
authors.lastname: Ridker
authors.forename: Charles
authors.initials: C
authors.lastname: Poole
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Murabito
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Widen
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Ken K
authors.initials: KK
authors.lastname: Ong
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000367:Age Factors; D015992:Body Mass Index; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D015810:Linkage Disequilibrium; D008572:Menarche / Q000235:genetics*; D009765:Obesity / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055105:Waist Circumference; D049629:Waist-Hip Ratio; D044465:White People / Q000235:genetics*; D016387:Women's Health / Q000706:statistics & numerical data
keywords: adiposity; body mass index; genetic association studies; menarche; obesity; waist circumference; waist:hip ratio; women's health
references.citation: Obesity (Silver Spring). 2010 Apr;18(4):803-8
references.pmid: 19851299
references.citation: Nat Genet. 2008 Jun;40(6):768-75
references.pmid: 18454148
references.citation: Nat Genet. 2009 Jan;41(1):25-34
references.pmid: 19079261
references.citation: Int J Obes (Lond). 2006 Nov;30(11):1595-600
references.pmid: 16568135
references.citation: Diabetologia. 2012 Mar;55(3):681-8
references.pmid: 22170465
references.citation: Hum Biol. 1995 Oct;67(5):739-53
references.pmid: 8543288
references.citation: Endocrinol Metab Clin North Am. 1997 Dec;26(4):893-912
references.pmid: 9429864
references.citation: PLoS Med. 2007 Apr;4(4):e132
references.pmid: 17455989
references.citation: PLoS Genet. 2009 Jun;5(6):e1000539
references.pmid: 19557197
references.citation: Diabetes. 2010 Nov;59(11):2980-8
references.pmid: 20724581
references.citation: Am J Epidemiol. 2007 Dec 15;166(12):1431-7
references.pmid: 17875585
references.citation: Am J Epidemiol. 2002 Apr 1;155(7):672-9
references.pmid: 11914195
references.citation: Int J Obes (Lond). 2005 Sep;29 Suppl 2:S97-100
references.pmid: 16385759
references.citation: Am J Epidemiol. 1989 Apr;129(4):687-702
references.pmid: 2646917
references.citation: BMC Med Genet. 2007 Sep 19;8 Suppl 1:S18
references.pmid: 17903300
references.citation: Lancet. 2011 Feb 12;377(9765):557-67
references.pmid: 21295846
references.citation: Science. 2007 May 11;316(5826):889-94
references.pmid: 17434869
references.citation: Nucleic Acids Res. 2011 Jul;39(Web Server issue):W307-15
references.pmid: 21646343
references.citation: Nat Genet. 2010 Nov;42(11):949-60
references.pmid: 20935629
references.citation: Clin Chem. 2008 Feb;54(2):249-55
references.pmid: 18070814
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W193-200
references.pmid: 17478515
references.citation: Nat Genet. 2009 Jun;41(6):648-50
references.pmid: 19448620
references.citation: Nat Genet. 2010 Nov;42(11):937-48
references.pmid: 20935630
references.citation: Nat Genet. 2009 Jun;41(6):724-8
references.pmid: 19448621
references.citation: Obesity (Silver Spring). 2009 Dec;17(12):2254-7
references.pmid: 19478790
references.citation: Bioinformatics. 2008 Dec 15;24(24):2938-9
references.pmid: 18974171
references.citation: Breast Dis. 2005-2006;24:17-35
references.pmid: 16917137
references.citation: Science. 1978 Jun 30;200(4349):1509-13
references.pmid: 17757694
references.citation: Breast Cancer Res. 2012 Mar 20;14(2):R54
references.pmid: 22433456
references.citation: J Obes. 2011;2011:180729
references.pmid: 21773002
references.citation: Nat Genet. 2009 Jun;41(6):734-8
references.pmid: 19448622
references.citation: Trends Endocrinol Metab. 2009 Jul;20(5):237-42
references.pmid: 19541497
references.citation: Mol Cell Endocrinol. 2006 Jul 25;254-255:172-8
references.pmid: 16806671
references.citation: Science. 1970 Jul 24;169(3943):397-9
references.pmid: 5450378
references.citation: PLoS Genet. 2012;8(3):e1002607
references.pmid: 22479202
references.citation: PLoS Genet. 2009 Jun;5(6):e1000508
references.pmid: 19557161
references.citation: PLoS Genet. 2011 Jan 13;7(1):e1001273
references.pmid: 21249183
references.citation: Int J Obes. 1987;11(4):347-55
references.pmid: 3312052
references.citation: Bioinformatics. 2010 Sep 1;26(17):2190-1
references.pmid: 20616382
references.citation: Nat Genet. 2010 Dec;42(12):1077-85
references.pmid: 21102462
references.citation: Genome Biol. 2011;12(2):104
references.pmid: 21349207
references.citation: Twin Res Hum Genet. 2010 Apr;13(2):179-93
references.pmid: 20397748
references.citation: Am J Clin Nutr. 2010 Jan;91(1):284S-288S
references.pmid: 19906804
references.citation: Pediatrics. 2002 Oct;110(4):e43
references.pmid: 12359816
references.citation: Ann N Y Acad Sci. 2008;1135:265-79
references.pmid: 18574233
references.citation: Am J Epidemiol. 2010 Feb 1;171(3):334-44
references.pmid: 20026580
references.citation: Nat Genet. 2008 Jun;40(6):716-8
references.pmid: 18454146
references.citation: PLoS Genet. 2009 Mar;5(3):e1000420
references.pmid: 19282985
references.citation: Nat Genet. 2009 Jan;41(1):18-24
references.pmid: 19079260