The association between weight, height, and head circumference reconsidered

Scheffler, Christiane; Greil, Holle; Hermanussen, Michael

doi:10.1038/pr.2017.3

Cited by 20 publications

(16 citation statements)

References 12 publications

(5 reference statements)

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“…Studies of body growth and brain development suggest that brain size is not determined by body size (27). Furthermore, a recent study of 14,819 children under 7 years of age found that after the age of 2 head growth seemed to progress independently of skeletal growth and body size (28). Therefore, different mechanisms may underlie the observed restricted brain and body development.…”

Section: Discussionmentioning

confidence: 99%

Total brain, cortical, and white matter volumes in children previously treated with glucocorticoids

et al. 2018

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BackgroundPerinatal exposure to glucocorticoids and elevated endogenous glucocorticoid levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid treatment during childhood on brain volumes.MethodsA total of 30 children and adolescents with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical gray and white matter, brain, intracranial volume, and total cortical thickness and surface area were derived from MRI scans.ResultsPatients had significantly smaller gray and white matter and total brain volumes relative to healthy controls. Brain volume differences disappeared when accounting for intracranial volume, as patients had relatively smaller intracranial volumes. Group differences were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures.ConclusionObserved smaller total brain, cortical gray, and white matter volumes in children and adolescents previously treated with glucocorticoids compared with that in healthy controls may reflect both developmental and degenerative processes. Prospective longitudinal studies are warranted to clarify whether findings are related to treatment or disease.

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Section: Discussionmentioning

confidence: 99%

Total brain, cortical, and white matter volumes in children previously treated with glucocorticoids

et al. 2018

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“…We believe that the replication results imply important clues towards true associations. Second, the unbalanced sample sizes used in the MTAG analysis may elevate false positive rate, as described by the MTAG authors (Scheffler et al, 2017). We tackled this issue by monitoring both the original and the integrative association signals for any unusual difference (e.g., non- to extreme significance).…”

Section: Discussionmentioning

confidence: 99%

“…Many studies attempt to define some conceptual growth parameters by integrating the three traits to comprehensively reflect children’s health status (Sankilampi et al, 2013; Haksari et al, 2016). Their high phenotypic correlation (Scheffler et al, 2017) implies that these traits may share some common genetic architecture.…”

Section: Introductionmentioning

confidence: 99%

Three Novel Loci for Infant Head Circumference Identified by a Joint Association Analysis

Yang

Zhang

et al. 2019

Front. Genet.

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As an important trait at birth, infant head circumference (HC) is associated with a variety of intelligence- and mental-related conditions. Despite being dominated by genetics, the mechanism underlying the variation of HC is poorly understood. Aiming to uncover the genetic basis of HC, we performed a genome-wide joint association analysis by integrating the genome-wide association summary statistics of HC with that of its two related traits, birth length and birth weight, using a recently developed integrative method, multitrait analysis of genome-wide association (MTAG), and performed in silico replication in an independent sample of intracranial volume (N = 26,577). We then conducted a series of bioinformatic investigations on the identified loci. Combining the evidence from both the MTAG analysis and the in silico replication, we identified three novel loci at the genome-wide significance level (α = 5.0 × 10−8): 3q23 [lead single nucleotide polymorphism (SNP) rs9846396, p MTAG = 3.35 × 10−8, p replication = 0.01], 7p15.3 (rs12534093, p MTAG = 2.00 × 10−8, p replication = 0.004), and 9q33.3 (rs7048271 p MTAG = 9.23 × 10−10, p replication = 1.14 × 10−4). Each of the three lead SNPs was associated with at least one of eight brain-related traits including intelligence and educational attainment. Credible risk variants, defined as those SNPs located within 500 kb of the lead SNP and with p values within two orders of magnitude of the lead SNP, were enriched in DNase I hypersensitive site region in brain. Nine candidate genes were prioritized at the three novel loci using multiple sources of information. Gene set enrichment analysis identified one associated pathway GO:0048009, which participates in the development of nervous system. Our findings provide useful insights into the genetic basis of HC and the relationship between brain growth and mental health.

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“…The observation that final HC is largely determined by the age of 6 years in a large study from the UK 7 is therefore likely to be valid in multiple populations. In addition, nutritional status, body size, and HC are closely correlated for healthy children during early life, and become less related after 24 months of age 8 . While HC properties in early childhood have immediate medical relevance, there are also compelling reasons to study HC in adulthood.…”

Section: Introductionmentioning

confidence: 99%

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

et al. 2019

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Cranial growth and development is a complex process which affects the closely related traits of head circumference (HC) and intracranial volume (ICV). The underlying genetic influences shaping these traits during the transition from childhood to adulthood are little understood, but might include both age-specific genetic factors and low-frequency genetic variation. Here, we model the developmental genetic architecture of HC, showing this is genetically stable and correlated with genetic determinants of ICV. Investigating up to 46,000 children and adults of European descent, we identify association with final HC and/or final ICV + HC at 9 novel common and low-frequency loci, illustrating that genetic variation from a wide allele frequency spectrum contributes to cranial growth. The largest effects are reported for low-frequency variants within TP53, with 0.5 cm wider heads in increaser-allele carriers versus non-carriers during mid-childhood, suggesting a previously unrecognized role of TP53 transcripts in human cranial development.

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The association between weight, height, and head circumference reconsidered

Abstract: Under appropriate nutritional and health circumstances, nutritional status, body size, and head circumference are not related.

Cited by 20 publications

References 12 publications

Total brain, cortical, and white matter volumes in children previously treated with glucocorticoids

Total brain, cortical, and white matter volumes in children previously treated with glucocorticoids

Three Novel Loci for Infant Head Circumference Identified by a Joint Association Analysis

Low-frequency variation in TP53 has large effects on head circumference and intracranial volume

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