Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
Copyright policy )Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
- University of Minnesota System United States
- National University of Singapore Singapore
- National Academies of Sciences, Engineering, and Medicine United States
- Massachusetts Institute of Technology United States
- University of Edinburgh United Kingdom
Netherlands Twin Register (NTR), Aging, Body Height: genetic, Time Factors, Inheritance Patterns, Body Size: genetic, Genetic Loci: genetic, Body Size, Child, genome wide association study, DNA Copy Number Variation, Adolescent; Aging; Body Height; Body Size; Child; DNA Copy Number Variations; Female; Genetic Loci; Genetic Predisposition to Disease; Humans; Inheritance Patterns; Menarche; Obesity; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Reproducibility of Results; Time Factors; Genome-Wide Association Study; Genetics, Menarche: genetic, Single Nucleotide, DNA Copy Number Variations: genetic, Female, Human, Quantitative Trait Loci: genetic, 572, Adolescent, DNA Copy Number Variations, Quantitative Trait Loci, 610, Reproducibility of Result, Single Nucleotide: genetic, EMC MM-01-52-07, Polymorphism, Single Nucleotide, Sequence variants, 1311 Genetics, genome wide association study; age at menarche, age at menarche, Energy-balance, 616, GIANT Consortium, Aging: physiology, Humans, Genetic Predisposition to Disease, Obesity, Polymorphism, Inheritance Patterns: genetic, Inheritance Pattern, Menarche, Puberty, Obesity: genetic, Reproducibility of Results, Adolescent; Aging; Aging: physiology; Body Height; Body Height: genetics; Body Size; Body Size: genetics; Child; DNA Copy Number Variations; DNA Copy Number Variations: genetics; Female; Genetic Loci; Genetic Loci: genetics; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Inheritance Patterns; Inheritance Patterns: genetics; Menarche; Menarche: genetics; Obesity; Obesity: genetics; Polymorphism; Quantitative Trait Loci; Quantitative Trait Loci: genetics; Reproducibility of Results; Single Nucleotide; Single Nucleotide: genetics; Time Factors, Body Height, EMC MM-01-39-04, Adolescent; Aging/physiology; Body Height/genetics; Body Size/genetics; Child; DNA Copy Number Variations/genetics; Female; Genetic Loci/genetics; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Inheritance Patterns/genetics; Menarche/genetics; Obesity/genetics; Polymorphism, Single Nucleotide/genetics; Quantitative Trait Loci/genetics; Reproducibility of Results; Time Factors ; Colaus Study, EMC MM-01-39-02, Genetic Loci, Genome-Wide Association Study
Netherlands Twin Register (NTR), Aging, Body Height: genetic, Time Factors, Inheritance Patterns, Body Size: genetic, Genetic Loci: genetic, Body Size, Child, genome wide association study, DNA Copy Number Variation, Adolescent; Aging; Body Height; Body Size; Child; DNA Copy Number Variations; Female; Genetic Loci; Genetic Predisposition to Disease; Humans; Inheritance Patterns; Menarche; Obesity; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Reproducibility of Results; Time Factors; Genome-Wide Association Study; Genetics, Menarche: genetic, Single Nucleotide, DNA Copy Number Variations: genetic, Female, Human, Quantitative Trait Loci: genetic, 572, Adolescent, DNA Copy Number Variations, Quantitative Trait Loci, 610, Reproducibility of Result, Single Nucleotide: genetic, EMC MM-01-52-07, Polymorphism, Single Nucleotide, Sequence variants, 1311 Genetics, genome wide association study; age at menarche, age at menarche, Energy-balance, 616, GIANT Consortium, Aging: physiology, Humans, Genetic Predisposition to Disease, Obesity, Polymorphism, Inheritance Patterns: genetic, Inheritance Pattern, Menarche, Puberty, Obesity: genetic, Reproducibility of Results, Adolescent; Aging; Aging: physiology; Body Height; Body Height: genetics; Body Size; Body Size: genetics; Child; DNA Copy Number Variations; DNA Copy Number Variations: genetics; Female; Genetic Loci; Genetic Loci: genetics; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Inheritance Patterns; Inheritance Patterns: genetics; Menarche; Menarche: genetics; Obesity; Obesity: genetics; Polymorphism; Quantitative Trait Loci; Quantitative Trait Loci: genetics; Reproducibility of Results; Single Nucleotide; Single Nucleotide: genetics; Time Factors, Body Height, EMC MM-01-39-04, Adolescent; Aging/physiology; Body Height/genetics; Body Size/genetics; Child; DNA Copy Number Variations/genetics; Female; Genetic Loci/genetics; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Inheritance Patterns/genetics; Menarche/genetics; Obesity/genetics; Polymorphism, Single Nucleotide/genetics; Quantitative Trait Loci/genetics; Reproducibility of Results; Time Factors ; Colaus Study, EMC MM-01-39-02, Genetic Loci, Genome-Wide Association Study
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