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Prepubertal Dietary and Plasma Phospholipid Fatty Acids Related to Puberty Timing: Longitudinal Cohort and Mendelian Randomization Analyses.

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Day, Felix R 
Perry, John RB 
Luan, Jian'an 
Langenberg, Claudia 


Dietary intakes of polyunsaturated, monounsaturated and saturated fatty acids (FAs) have been inconsistently associated with puberty timing. We examined longitudinal associations of prepubertal dietary and plasma phospholipid FAs with several puberty timing traits in boys and girls. In the Avon Longitudinal Study of Parents and Children, prepubertal fat intakes at 3-7.5 years and plasma phospholipid FAs at 7.5 years were measured. Timings of Tanner stage 2 genital or breast development and voice breaking or menarche from repeated reports at 8-17 years, and age at peak height velocity (PHV) from repeated height measurements at 5-20 years were estimated. In linear regression models with adjustment for maternal and infant characteristics, dietary substitution of polyunsaturated FAs for saturated FAs, and higher concentrations of dihomo-γ-linolenic acid (20:3n6) and palmitoleic acid (16:1n7) were associated with earlier timing of puberty traits in girls (n = 3872) but not boys (n = 3654). In Mendelian Randomization models, higher genetically predicted circulating dihomo-γ-linolenic acid was associated with earlier menarche in girls. Based on repeated dietary intake data, objectively measured FAs and genetic causal inference, these findings suggest that dietary and endogenous metabolic pathways that increase plasma dihomo-γ-linolenic acid, an intermediate metabolite of n-6 polyunsaturated FAs, may promote earlier puberty timing in girls.



ALSPAC, Mendelian Randomization, fatty acids, prospective study, puberty timing, Adolescent, Adult, Age Factors, Child, Child, Preschool, Cohort Studies, Diet, Fatty Acids, Female, Humans, Longitudinal Studies, Male, Mendelian Randomization Analysis, Phospholipids, Puberty, Time, Young Adult

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MRC (MC_UU_00006/2)
MRC (MC_UU_00006/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MC_UU_12015/1)
Medical Research Council (MC_UU_12015/2)
Medical Research Council (MC_UU_12015/3)
MRC (MC_UU_00006/3)
Department of Health (via National Institute for Health Research (NIHR)) (NIHR202397)
National Institute for Health and Care Research (IS-BRC-1215-20014)
: This work was supported by the Medical Research Council (Unit programmes: MC_UU_00006/2, MC_UU_00006/3 and MC_UU_00006/2) and the NIHR Biomedical Research Centre Cambridge: Nutrition, Diet, and Lifestyle Research Theme (IS-BRC-1215-20014). The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website ( The included ALSPAC data were specifically funded by the intramural research programme of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) with funding from the National Oceanic and Atmospheric Administration (NOAA) to the assays of child’s blood, and the Center for Disease Control (AY5350) to pubertal assessments.