1. Genome-wide association study of age at menarche in African-American women
- Author
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Charles Kooperberg, Nancy Fugate Woods, Sandra L. Deming, Joel N. Hirschhorn, Kari E. North, Elisa V. Bandera, Erin N. Smith, Christopher A. Haiman, Zhao Chen, Michael F. Press, Leslie Bernstein, Sarah S. Murray, Loic Le Marchand, Alice M. Arnold, Robert C. Millikan, Sathanur R. Srinivasan, Laurence N. Kolonel, Esther M. John, Julie R. Palmer, Nora Franceschini, Gary Chen, Christine B. Ambrosone, Gerald S. Berenson, Regina G. Ziegler, Ellen W. Demerath, Zofia K. Z. Gajdos, Gerardo Heiss, Joanne M. Murabito, Jorge L. Rodriquez-Gil, Anne R. Cappola, Stephen J. Chanock, Michelle K. Evans, Cathy E. Elks, Christina T. L. Chen, Sarah J. Nyante, L. Adrienne Cupples, Tomi Pastinen, Edward A. Ruiz-Narváez, B. Gwen Windham, Xiaoning Lu, Christopher S. Carlson, Ching-Ti Liu, Melissa Wellons, Jennifer J. Hu, Nicholas J. Schork, Angela Britton, Mike A. Nalls, Alan B. Zonderman, Wei Chen, Aleksandar Rajkovic, Sue A. Ingles, Nora L. Nock, Wei Zheng, Kathleen F. Kerr, Brian E. Henderson, and Solomon K. Musani
- Subjects
Aging ,Genome-wide association study ,Type 2 diabetes ,Medical and Health Sciences ,Risk Factors ,Group F ,2.1 Biological and endogenous factors ,Aetiology ,Child ,Genetics (clinical) ,Genetics ,African Americans ,Genetics & Heredity ,Membrane Glycoproteins ,Association Studies Articles ,Nuclear Receptor Subfamily 1, Group F, Member 1 ,General Medicine ,Single Nucleotide ,Biological Sciences ,Menarche ,Female ,Type 2 ,Member 1 ,Adolescent ,Nuclear Receptor Subfamily 1 ,Single-nucleotide polymorphism ,Locus (genetics) ,Biology ,Population stratification ,Polymorphism, Single Nucleotide ,White People ,Young Adult ,medicine ,Diabetes Mellitus ,SNP ,Humans ,Obesity ,Polymorphism ,Molecular Biology ,Whites ,Prevention ,Contraception/Reproduction ,Human Genome ,Membrane Proteins ,Genetic Variation ,medicine.disease ,Black or African American ,Diabetes Mellitus, Type 2 ,Genetic Loci ,Case-Control Studies ,Linear Models ,Demography ,Genome-Wide Association Study - 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.
- Published
- 2013