Recent progress in the study of the genetics of height

Lettre, Guillaume

doi:10.1007/s00439-011-0969-x

Cited by 78 publications

(63 citation statements)

References 46 publications

(29 reference statements)

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“…While stature is believed an example of a classic polygenic trait with high heritability, a recent GWAS study on the genetics underlying this trait reports a low percentage (~3-5%) of effect from most of the common variants (Weeden and Frayling, 2008) leaving some authors to recommend the study of diverse ethnicities and redefine the phenotype to that of height velocity (Lettre, 2011). Recent findings correlate variation in lipid profiles and bone loss, suggesting that these two functions are mutually constrained in some way, however, studies are inconclusive with some authors pointing at a paucity of studies examining ethnic variation (Tian L, Yu X, 2015).…”

Section: Discussionmentioning

confidence: 99%

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Mosher¹,

Melton²,

Stapleton³

et al. 2016

Human Biology

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DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA which are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process.Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative function includes regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism and Pre-print version. Visit http://digitalcommons.wayne.edu/humbiol/ after publication to acquire the final version.reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examines the significance of variation in DNA methylation patterns along the leptin core promoter in four populations and uses biomarkers reflecting leptin's functional process in two of those populations to investigate the relevance of the ethnic variation identified in the DNA methylation. Those two populations are the Western Buryats of Siberia and the Mennonites of Central Kansas.LEP's core promoter region contains both the C/EBPα transcription binding site (TBS) which tempers the final step in adipocyte maturity and capacity to synthesize leptin and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, with others suggesting tissue-specific methylation variation at this region. We hypothesize that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers which reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system and anthropometric measures.A distinct and consistent overall pattern of differential DNA methylation across seven CpG sites of LEP core promoter is documented in all ethnicities and both sexes in our combined analyses of 313 individuals. This pattern replicates those identified in previous studies, thus suggesting a conserved core promoter region across populations. The second analyses in two of the four ...

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Section: Discussionmentioning

confidence: 99%

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Mosher¹,

Melton²,

Stapleton³

et al. 2016

Human Biology

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“…To investigate if the significant SNPs detected in this study were within the range of previously identified QTL for relevant traits, we searched for meat or production QTL in the SheepQTLdb [28] within a 1-Mb region on both sides of each significant SNP.…”

Section: Methodsmentioning

confidence: 99%

Combined GWAS and ‘guilt by association’-based prioritization analysis identifies functional candidate genes for body size in sheep

et al. 2017

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BackgroundBody size in sheep is an important indicator of productivity, growth and health as well as of environmental adaptation. It is a composite quantitative trait that has been studied with high-throughput genomic methods, i.e. genome-wide association studies (GWAS) in various mammalian species. Several genomic markers have been associated with body size traits and genes have been identified as causative candidates in humans, dog and cattle. A limited number of related GWAS have been performed in various sheep breeds and have identified genomic regions and candidate genes that partly account for body size variability. Here, we conducted a GWAS in Frizarta dairy sheep with phenotypic data from 10 body size measurements and genotypic data (from Illumina ovineSNP50 BeadChip) for 459 ewes.ResultsThe 10 body size measurements were subjected to principal component analysis and three independent principal components (PC) were constructed, interpretable as width, height and length dimensions, respectively. The GWAS performed for each PC identified 11 significant SNPs, at the chromosome level, one on each of the chromosomes 3, 8, 9, 10, 11, 12, 19, 20, 23 and two on chromosome 25. Nine out of the 11 SNPs were located on previously identified quantitative trait loci for sheep meat, production or reproduction. One hundred and ninety-seven positional candidate genes within a 1-Mb distance from each significant SNP were found. A guilt-by-association-based (GBA) prioritization analysis (PA) was performed to identify the most plausible functional candidate genes. GBA-based PA identified 39 genes that were significantly associated with gene networks relevant to body size traits. Prioritized genes were identified in the vicinity of all significant SNPs except for those on chromosomes 10 and 12. The top five ranking genes were TP53, BMPR1A, PIK3R5, RPL26 and PRKDC.ConclusionsThe results of this GWAS provide evidence for 39 causative candidate genes across nine chromosomal regions for body size traits, some of which are novel and some are previously identified candidates from other studies (e.g. TP53, NTN1 and ZNF521). GBA-based PA has proved to be a useful tool to identify genes with increased biological relevance but it is subjected to certain limitations.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-017-0316-3) contains supplementary material, which is available to authorized users.

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“…Nevertheless, it is known that BMI is an imperfect indicator of weight distribution and body composition [5]. Whilst weight is a result of the balance of energy (intake and expenditure), height is considered an heritable human trait [6], influenced by environment, context, sociodemographic and economic determinants throughout life course [7,8]. Moreover, height is positively associated to wealth, success [9], and social status [7,10] while is inversely associated with some biological and behavioral determinants of cardiovascular disease [11,12,13].…”

Section: Introductionmentioning

confidence: 99%

Body Mass Index Categories and Attained Height in Portuguese Adults

et al. 2018

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Objective: To analyze the associations between height and BMI categories in a Portuguese representative sample. Methods: This is a cross-sectional study with a representative sample of 32,644 Portuguese adults (52.4% females). Sociodemographic and lifestyle characteristics were obtained along with self-reported height and weight. We performed generalized linear models to assess the differences in attained height across BMI categories; analyses were adjusted for age, gender, education, family income per month, proxy reporting information, dietary patterns, and smoking. Results: BMI categories included underweight and normal weight (46.4%), overweight (37.6%), obese class I and II (15.2%), and obese class III (0.8%). Adults with normal weight had a significantly higher height (females +7 cm and males +5 cm) when compared to obese class III. As BMI categories increased, height decreased. In females and males, after adjusting for confounders, estimates of attained height decreased when compared to the unadjusted model (β = -0.049, 95% CI = -0.050; -0.049 and β = -0.030, 95% CI = -0.031; -0.029, respectively), although they remained still significant. Conclusion: Our results suggest a significant difference in attained height between BMI categories. Future intervention programs aiming at preventing overweight and obesity should monitor sociodemographic, health and environmental conditions that affect attained height potential.

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Recent progress in the study of the genetics of height

Cited by 78 publications

References 46 publications

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Patterns of DNA Methylation across the Leptin Core Promoter in Four Diverse Asian and North American Populations

Combined GWAS and ‘guilt by association’-based prioritization analysis identifies functional candidate genes for body size in sheep

Body Mass Index Categories and Attained Height in Portuguese Adults

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