Responding to a 100-Year-Old Challenge from Fisher: A Biometrical Analysis of Adult Height in the NLSY Data Using Only Cousin Pairs

AbstractObjectivesAdequate treatment of congenital hypothyroidism (CH) is required for normal growth and sexual development. To evaluate pubertal development in patients with permanent CH detected by a statewide Neonatal Screening Program of Paraná and, secondly, to evaluate adult height (AH) in a subgroup of patients.MethodsClinical, laboratory, and auxological data obtained from medical records of 174 patients (123 girls).ResultsMedian chronological age (CA) at treatment initiation was 24 days, and mean initial levothyroxine dose was 11.7 ± 1.9 μg/kg/day; mean CA at puberty onset was 11.5 ± 1.3 years (boys) and 9.7 ± 1.2 years (girls); mean CA in girls who underwent menarche (n=81) was 12.1 ± 1.1 years. Thyroid-stimulating hormone (TSH) values above the normal range were observed in 36.4% of the boys and 32.7% of the girls on puberty onset, and in 44.6% around menarche. Among 15 boys and 66 girls who had reached the AH, the median height z-score value was significantly greater than the target height (TH) z-score value in boys (p=0.01) and in girls (p<0.001). Boys with normal TSH values at puberty onset had greater mean AH z-score compared with boys with TSH values above the normal range (p=0.04).ConclusionsIn this group, pubertal development in girls with CH was not different from that reported in healthy girls in the general Brazilian population. Boys with higher TSH at puberty onset may have an increased risk of not reaching their potential height compared with those with normal TSH during this period. In a subgroup who attained AH, the median AH z-score was greater than the median TH z-score.

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The effect of treatment with recombinant human growth hormone (rhGH) on linear growth and adult height in children with idiopathic short stature (ISS): a systematic review and meta-analysis

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0287 ◽

2020 ◽

Vol 33 (12) ◽

pp. 1577-1588

Author(s):

George Paltoglou ◽

Ioannis Dimitropoulos ◽

Georgia Kourlaba ◽

Evangelia Charmandari

Keyword(s):

Systematic Review ◽

Growth Hormone ◽

Short Stature ◽

Human Growth Hormone ◽

Adult Height ◽

Linear Growth ◽

Meta Analysis ◽

Recombinant Human Growth Hormone ◽

Human Growth ◽

Idiopathic Short Stature

AbstractObjectivesIdiopathic short stature (ISS) is a recognized, albeit a controversial indication for treatment with recombinant human growth hormone (rhGH).The objective of the present study was to conduct a systematic review of the literature and meta-analyses of selected studies about the use of rhGH in children with ISS on linear growth and adult height (AH).MethodsA systematic literature search was conducted to identify relevant studies published till February 28, 2017 in the following databases: Medline (PubMed), Scopus and Cochrane Central Registry of Controlled Trials. After exclusion of duplicate studies, 3,609 studies were initially identified. Of those, 3,497 studies were excluded during the process of assessing the title and/or the abstract. The remaining 112 studies were evaluated further by assessing the full text; 21 of them fulfilled all the criteria in order to be included in the current meta-analysis.ResultsChildren who received rhGH had significantly higher height increment at the end of the first year, an effect that persisted in the second year of treatment and achieved significantly higher AH than the control group. The difference between the two groups was equal to 5.3 cm (95% CI: 3.4–7 cm) for male and 4.7 cm (95% CI: 3.1–6.3 cm) for female patients.ConclusionIn children with ISS, treatment with rhGH improves short-term linear growth and increases AH compared with control subjects. However, the final decision should be made on an individual basis, following detailed diagnostic evaluation and careful consideration of both risks and benefits of rhGH administration.

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Growth in achondroplasia, from birth to adulthood, analysed by the JPA-2 model

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0298 ◽

2020 ◽

Vol 33 (12) ◽

pp. 1589-1595

Author(s):

Mariana del Pino ◽

Virginia Fano ◽

Paula Adamo

Keyword(s):

General Population ◽

Growth Curve ◽

Growth Velocity ◽

Adult Height ◽

Growth Curves ◽

Peak Height ◽

Height Growth ◽

Individual Growth ◽

Height Velocity ◽

Peak Height Velocity

AbstractObjectivesIn general population, there are three phases in the human growth curve: infancy, childhood and puberty, with different main factors involved in their regulation and mathematical models to fit them. Achondroplasia children experience a fast decreasing growth during infancy and an “adolescent growth spurt”; however, there are no longitudinal studies that cover the analysis of the whole post-natal growth. Here we analyse the whole growth curve from infancy to adulthood applying the JPA-2 mathematical model.MethodsTwenty-seven patients, 17 girls and 10 boys with achondroplasia, who reached adult size, were included. Height growth data was collected from birth until adulthood. Individual growth curves were estimated by fitting the JPA-2 model to each individual’s height for age data.ResultsHeight growth velocity curves show that after a period of fast decreasing growth velocity since birth, with a mean of 9.7 cm/year at 1 year old, the growth velocity is stable in late preschool years, with a mean of 4.2 cm/year. In boys, age and peak height velocity in puberty were 13.75 years and 5.08 cm/year and reach a mean adult height of 130.52 cm. In girls, the age and peak height velocity in puberty were 11.1 years and 4.32 cm/year and reach a mean adult height of 119.2 cm.ConclusionsThe study of individual growth curves in achondroplasia children by the JPA-2 model shows the three periods, infancy, childhood and puberty, with a similar shape but lesser in magnitude than general population.

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The limits of normal approximation for adult height

European Journal of Human Genetics ◽

10.1038/s41431-021-00836-7 ◽

2021 ◽

Author(s):

Sergei A. Slavskii ◽

Ivan A. Kuznetsov ◽

Tatiana I. Shashkova ◽

Georgii A. Bazykin ◽

Tatiana I. Axenovich ◽

...

Keyword(s):

Complex Traits ◽

Adult Height ◽

Normal Approximation ◽

Classical Model ◽

Model Complexity ◽

Test Case ◽

Genetic Studies ◽

Quantitative Genetic ◽

Profound Influence ◽

Log Normal

AbstractAdult height inspired the first biometrical and quantitative genetic studies and is a test-case trait for understanding heritability. The studies of height led to formulation of the classical polygenic model, that has a profound influence on the way we view and analyse complex traits. An essential part of the classical model is an assumption of additivity of effects and normality of the distribution of the residuals. However, it may be expected that the normal approximation will become insufficient in bigger studies. Here, we demonstrate that when the height of hundreds of thousands of individuals is analysed, the model complexity needs to be increased to include non-additive interactions between sex, environment and genes. Alternatively, the use of log-normal approximation allowed us to still use the additive effects model. These findings are important for future genetic and methodologic studies that make use of adult height as an exemplar trait.

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The Relationship between Adult Height and Blood Pressure

Cardiology ◽

10.1159/000514205 ◽

2021 ◽

pp. 1-6

Author(s):

John Michael Cochran ◽

Vincent R. Siebert ◽

Jeffrey Bates ◽

Djenita Butulija ◽

Anna Kolpakchi ◽

...

Keyword(s):

Blood Pressure ◽

Cardiovascular Disease ◽

Adult Height ◽

Augmentation Index ◽

Epidemiological Data ◽

Systemic Review ◽

Inverse Association ◽

Literature Evidence ◽

Artery Disease ◽

The Relationship

Background: Identification and modification of cardiovascular risk factors is paramount to reducing cardiovascular disease morbidity and mortality. Hypertension is a major risk factor for cardiovascular disease, but its association with height remains largely underrecognized. Objectives: The objective of this manuscript is to review the evidence examining the association between blood pressure and human stature and to summarize the plausible pathophysiological mechanisms behind such an association. Methods: A systematic review of adult human height and its association with hypertension and coronary artery disease was undertaken. The literature evidence is summarized and tabulated, and an overview of the pathophysiological basis for this association is presented. Results: Shorter arterial lengths found in shorter individuals may predispose to hypertension in a complex hemodynamic interplay, which is explained predominantly by summated arterial wave reflections and an elevated augmentation index. Our systemic review suggests that an inverse relationship between adult height and blood pressure exists. However, differences in the studied populations and heterogeneity in the methods applied across the various studies limit the generalizability of these findings and their clinical application. Conclusion: Physiological studies and epidemiological data suggest a potential inverse association between adult height and blood pressure. Further research is required to define the relationship more clearly between adult height and blood pressure and to assess whether antihypertensive therapeutic approaches and goals should be modified according to patients’ heights.

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