Back to Search
Start Over
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
- Publisher :
- Springer Science and Business Media LLC
-
Abstract
- Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.
- Subjects :
- Male
Parents
Hypothalamo-Hypophyseal System
Adolescent
Receptors, Retinoic Acid
Ubiquitin-Protein Ligases
Quantitative Trait Loci
Breast Neoplasms
Polymorphism, Single Nucleotide
Body Mass Index
Genomic Imprinting
Potassium Channels, Tandem Pore Domain
Humans
Obesity
Child
Alleles
2. Zero hunger
Menarche
Calcium-Binding Proteins
Ovary
Age Factors
Membrane Proteins
Proteins
3. Good health
Europe
Diabetes Mellitus, Type 2
Receptors, GABA-B
Ribonucleoproteins
Cardiovascular Diseases
Genetic Loci
Intercellular Signaling Peptides and Proteins
Female
Genome-Wide Association Study
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........9fa5d2c2d289f9a3ea928417f1018c7f