Influence of puberty timing on adiposity and cardiometabolic traits: A Mendelian randomisation study.
<h4>Background</h4>Earlier puberty is widely linked with future obesity and cardiometabolic disease. We examined whether age at puberty onset likely influences adiposity and cardiometabolic traits independent of childhood adiposity.<h4>Methods and findings</h4>One-sample Mend...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-08-01
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| Series: | PLoS Medicine |
| Online Access: | https://doi.org/10.1371/journal.pmed.1002641 |
| _version_ | 1818317140376158208 |
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| author | Joshua A Bell David Carslake Kaitlin H Wade Rebecca C Richmond Ryan J Langdon Emma E Vincent Michael V Holmes Nicholas J Timpson George Davey Smith |
| author_facet | Joshua A Bell David Carslake Kaitlin H Wade Rebecca C Richmond Ryan J Langdon Emma E Vincent Michael V Holmes Nicholas J Timpson George Davey Smith |
| author_sort | Joshua A Bell |
| collection | DOAJ |
| description | <h4>Background</h4>Earlier puberty is widely linked with future obesity and cardiometabolic disease. We examined whether age at puberty onset likely influences adiposity and cardiometabolic traits independent of childhood adiposity.<h4>Methods and findings</h4>One-sample Mendelian randomisation (MR) analyses were conducted on up to 3,611 white-European female and male offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort recruited at birth via mothers between 1 April 1991 and 31 December 1992. Time-sensitive exposures were age at menarche and age at voice breaking. Outcomes measured at age 18 y were body mass index (BMI), dual-energy X-ray absorptiometry-based fat and lean mass indices, blood pressure, and 230 cardiometabolic traits derived from targeted metabolomics (150 concentrations plus 80 ratios from nuclear magnetic resonance [NMR] spectroscopy covering lipoprotein subclasses of cholesterol and triglycerides, amino acids, inflammatory glycoproteins, and others). Adjustment was made for pre-pubertal BMI measured at age 8 y. For negative control MR analyses, BMI and cardiometabolic trait measures taken at age 8 y (before puberty, and which therefore cannot be an outcome of puberty itself) were used. For replication analyses, 2-sample MR was conducted using summary genome-wide association study data on up to 322,154 adults for post-pubertal BMI, 24,925 adults for post-pubertal NMR cardiometabolic traits, and 13,848 children for pre-pubertal obesity (negative control). Like observational estimates, 1-sample MR estimates in ALSPAC using 351 polymorphisms for age at menarche (explaining 10.6% of variance) among 2,053 females suggested that later age at menarche (per year) was associated with -1.38 kg/m2 of BMI at age 18 y (or -0.34 SD units, 95% CI -0.46, -0.23; P = 9.77 × 10-09). This coefficient attenuated 10-fold upon adjustment for BMI at age 8 y, to -0.12 kg/m2 (or -0.03 SDs, 95% CI -0.13, 0.07; P = 0.55). Associations with blood pressure were similar, but associations across other traits were small and inconsistent. In negative control MR analyses, later age at menarche was associated with -0.77 kg/m2 of pre-pubertal BMI measured at age 8 y (or -0.39 SDs, 95% CI -0.50, -0.29; P = 6.28 × 10-13), indicating that variants influencing menarche also influence BMI before menarche. Cardiometabolic trait associations were weaker and less consistent among males and both sexes combined. Higher BMI at age 8 y (per 1 kg/m2 using 95 polymorphisms for BMI explaining 3.4% of variance) was associated with earlier menarche among 2,648 females (by -0.26 y, 95% CI -0.37, -0.16; P = 1.16 × 10-06), likewise among males and both sexes combined. In 2-sample MR analyses using 234 polymorphisms and inverse variance weighted (IVW) regression, each year later age at menarche was associated with -0.81 kg/m2 of adult BMI (or -0.17 SD units, 95% CI -0.21, -0.12; P = 4.00 × 10-15). Associations were weaker with cardiometabolic traits. Using 202 polymorphisms, later menarche was associated with lower odds of childhood obesity (IVW-based odds ratio = 0.52 per year later, 95% CI 0.48, 0.57; P = 6.64 × 10-15). Study limitations include modest sample sizes for 1-sample MR, lack of inference to non-white-European populations, potential selection bias through modest completion rates of puberty questionnaires, and likely disproportionate measurement error of exposures by sex. The cardiometabolic traits examined were heavily lipid-focused and did not include hormone-related traits such as insulin and insulin-like growth factors.<h4>Conclusions</h4>Our results suggest that puberty timing has a small influence on adiposity and cardiometabolic traits and that preventive interventions should instead focus on reducing childhood adiposity. |
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| institution | Directory Open Access Journal |
| issn | 1549-1277 1549-1676 |
| language | English |
| last_indexed | 2024-12-13T09:32:35Z |
| publishDate | 2018-08-01 |
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| series | PLoS Medicine |
| spelling | doaj.art-6bfa0589cf1f466c9309b0e9931a49442022-12-21T23:52:26ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762018-08-01158e100264110.1371/journal.pmed.1002641Influence of puberty timing on adiposity and cardiometabolic traits: A Mendelian randomisation study.Joshua A BellDavid CarslakeKaitlin H WadeRebecca C RichmondRyan J LangdonEmma E VincentMichael V HolmesNicholas J TimpsonGeorge Davey Smith<h4>Background</h4>Earlier puberty is widely linked with future obesity and cardiometabolic disease. We examined whether age at puberty onset likely influences adiposity and cardiometabolic traits independent of childhood adiposity.<h4>Methods and findings</h4>One-sample Mendelian randomisation (MR) analyses were conducted on up to 3,611 white-European female and male offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort recruited at birth via mothers between 1 April 1991 and 31 December 1992. Time-sensitive exposures were age at menarche and age at voice breaking. Outcomes measured at age 18 y were body mass index (BMI), dual-energy X-ray absorptiometry-based fat and lean mass indices, blood pressure, and 230 cardiometabolic traits derived from targeted metabolomics (150 concentrations plus 80 ratios from nuclear magnetic resonance [NMR] spectroscopy covering lipoprotein subclasses of cholesterol and triglycerides, amino acids, inflammatory glycoproteins, and others). Adjustment was made for pre-pubertal BMI measured at age 8 y. For negative control MR analyses, BMI and cardiometabolic trait measures taken at age 8 y (before puberty, and which therefore cannot be an outcome of puberty itself) were used. For replication analyses, 2-sample MR was conducted using summary genome-wide association study data on up to 322,154 adults for post-pubertal BMI, 24,925 adults for post-pubertal NMR cardiometabolic traits, and 13,848 children for pre-pubertal obesity (negative control). Like observational estimates, 1-sample MR estimates in ALSPAC using 351 polymorphisms for age at menarche (explaining 10.6% of variance) among 2,053 females suggested that later age at menarche (per year) was associated with -1.38 kg/m2 of BMI at age 18 y (or -0.34 SD units, 95% CI -0.46, -0.23; P = 9.77 × 10-09). This coefficient attenuated 10-fold upon adjustment for BMI at age 8 y, to -0.12 kg/m2 (or -0.03 SDs, 95% CI -0.13, 0.07; P = 0.55). Associations with blood pressure were similar, but associations across other traits were small and inconsistent. In negative control MR analyses, later age at menarche was associated with -0.77 kg/m2 of pre-pubertal BMI measured at age 8 y (or -0.39 SDs, 95% CI -0.50, -0.29; P = 6.28 × 10-13), indicating that variants influencing menarche also influence BMI before menarche. Cardiometabolic trait associations were weaker and less consistent among males and both sexes combined. Higher BMI at age 8 y (per 1 kg/m2 using 95 polymorphisms for BMI explaining 3.4% of variance) was associated with earlier menarche among 2,648 females (by -0.26 y, 95% CI -0.37, -0.16; P = 1.16 × 10-06), likewise among males and both sexes combined. In 2-sample MR analyses using 234 polymorphisms and inverse variance weighted (IVW) regression, each year later age at menarche was associated with -0.81 kg/m2 of adult BMI (or -0.17 SD units, 95% CI -0.21, -0.12; P = 4.00 × 10-15). Associations were weaker with cardiometabolic traits. Using 202 polymorphisms, later menarche was associated with lower odds of childhood obesity (IVW-based odds ratio = 0.52 per year later, 95% CI 0.48, 0.57; P = 6.64 × 10-15). Study limitations include modest sample sizes for 1-sample MR, lack of inference to non-white-European populations, potential selection bias through modest completion rates of puberty questionnaires, and likely disproportionate measurement error of exposures by sex. The cardiometabolic traits examined were heavily lipid-focused and did not include hormone-related traits such as insulin and insulin-like growth factors.<h4>Conclusions</h4>Our results suggest that puberty timing has a small influence on adiposity and cardiometabolic traits and that preventive interventions should instead focus on reducing childhood adiposity.https://doi.org/10.1371/journal.pmed.1002641 |
| spellingShingle | Joshua A Bell David Carslake Kaitlin H Wade Rebecca C Richmond Ryan J Langdon Emma E Vincent Michael V Holmes Nicholas J Timpson George Davey Smith Influence of puberty timing on adiposity and cardiometabolic traits: A Mendelian randomisation study. PLoS Medicine |
| title | Influence of puberty timing on adiposity and cardiometabolic traits: A Mendelian randomisation study. |
| title_full | Influence of puberty timing on adiposity and cardiometabolic traits: A Mendelian randomisation study. |
| title_fullStr | Influence of puberty timing on adiposity and cardiometabolic traits: A Mendelian randomisation study. |
| title_full_unstemmed | Influence of puberty timing on adiposity and cardiometabolic traits: A Mendelian randomisation study. |
| title_short | Influence of puberty timing on adiposity and cardiometabolic traits: A Mendelian randomisation study. |
| title_sort | influence of puberty timing on adiposity and cardiometabolic traits a mendelian randomisation study |
| url | https://doi.org/10.1371/journal.pmed.1002641 |
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