# Genetic correlation and Mendelian randomization analyses support causal relationships between dietary habits and age at menarche

**Authors:** Ruilong Guo, Ruoyang Feng, Jiong Yang, Yanfeng Xiao, Chunyan Yin

PMC · DOI: 10.1038/s41598-024-58999-4 · 2024-04-10

## TL;DR

This study finds that certain dietary habits may influence the age at which girls start menstruating, based on genetic evidence.

## Contribution

The study provides novel causal evidence linking specific dietary habits to age at menarche using genetic correlation and Mendelian randomization.

## Key findings

- Genetic correlations were found between 29 dietary habits and age at menarche.
- Mendelian randomization identified 19 dietary habits significantly associated with age at menarche.
- Results were stable under sensitivity analysis, supporting the causal relationship.

## Abstract

Dietary habits are essential in the mean age at menarche (AAM). However, the causal relationship between these factors remains unclear. Therefore, this study aimed to elucidate the genetic relationship between dietary habits and AAM. Genetic summary statistics for dietary habits were obtained from the UK Biobank. GWAS summary data for AAM was obtained from the ReproGen Consortium. Linkage disequilibrium score regression was used to test genetic correlations between dietary habits and AAM. The Mendelian randomization (MR) analyses used the inverse-variance weighted method. Genetic correlations with AAM were identified for 29 candi-date dietary habits, such as milk type (skimmed, semi-skimmed, full cream; coefficient = 0.2704, Pldsc = 1.13 × 10−14). MR evaluations revealed that 19 dietary habits were associated with AAM, including bread type (white vs. any other; OR 1.71, 95% CI 1.28–2.29, Pmr = 3.20 × 10−4), tablespoons of cooked vegetables (OR 0.437, 95% CI 0.29–0.67; Pmr = 1.30 × 10−4), and cups of coffee per day (OR 0.72, 95% CI 0.57–0.92, Pmr = 8.31 × 10−3). These results were observed to be stable under the sensitivity analysis. Our study provides potential insights into the genetic mechanisms underlying AAM and evidence that dietary habits are associated with AAM.

## Full-text entities

- **Genes:** IGF2 (insulin like growth factor 2) [NCBI Gene 3481] {aka C11orf43, GRDF, IGF-II, PP9974, SRS3}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, KISS1 (KiSS-1 metastasis suppressor) [NCBI Gene 3814] {aka HH13, KiSS-1}, GNRH1 (gonadotropin releasing hormone 1) [NCBI Gene 2796] {aka GNRH, GRH, LHRH, LNRH}
- **Diseases:** cardiovascular, endocrine, and infertility (MESH:D002318), AAM (MESH:D019588), TS (MESH:D005879), precocious puberty (MESH:D011629), delayed pubertal development (MESH:D002658), chronic diseases (MESH:D002908), Obesity (MESH:D009765), osteoporosis (MESH:D010024), cancer (MESH:D009369), migraines (MESH:D008881), breast and endometrial cancer (MESH:C537243), deaths (MESH:D003643), estrogenic (MESH:D056828), breast cancer (MESH:D001943), acne (MESH:D000152)
- **Chemicals:** carbohydrates (MESH:D002241), margarine (MESH:D008383), caffeine (MESH:D002110), sterols (MESH:D013261), esters (MESH:D004952), lipids (MESH:D008055), trace elements (MESH:D014131), EEDs (-), luteinizing hormone (MESH:D007986), Isoflavones (MESH:D007529), salt (MESH:D012492), butter (MESH:D002079), dietary fat (MESH:D004041), sugar (MESH:D000073893), dihomo-gamma-linolenic acid (MESH:D015126), olive oil (MESH:D000069463)
- **Species:** Homo sapiens (human, species) [taxon 9606], Actinopterygii (fishes, superclass) [taxon 7898]
- **Cell lines:** S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11006932/full.md

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Source: https://tomesphere.com/paper/PMC11006932