scholarly journals Insights and Implications of Genome-Wide Association Studies of Height

2018 ◽  
Vol 103 (9) ◽  
pp. 3155-3168 ◽  
Author(s):  
Michael H Guo ◽  
Joel N Hirschhorn ◽  
Andrew Dauber
Keyword(s):  
Adult Height ◽  
Association Studies ◽  
Evidence Synthesis ◽  
Human Growth ◽  
Biological Pathways ◽  
Genome Wide Association ◽  
Growth Disorders ◽  
Genome Wide Association Studies ◽  
Growth Factor Signaling ◽  
Genome Wide

Abstract Context In the last decade, genome-wide association studies (GWASs) have catalyzed our understanding of the genetics of height and have identified hundreds of regions of the genome associated with adult height and other height-related body measurements. Evidence Acquisition GWASs related to height were identified via PubMed search and a review of the GWAS catalog. Evidence Synthesis The GWAS results demonstrate that height is highly polygenic: that is, many thousands of genetic variants distributed across the genome each contribute to an individual’s height. These height-associated regions of the genome are enriched for genes in known biological pathways involved in growth, such as fibroblast growth factor signaling, as well as for genes expressed in relevant tissues, such as the growth plate. GWASs can also uncover previously unappreciated biological pathways, such as theSTC2/PAPPA/IGFBP4 pathway. The genes implicated by GWASs are often the same genes that are the genetic causes of Mendelian growth disorders or skeletal dysplasias, and GWAS results can provide complementary information about these disorders. Conclusions Here, we review the rationale behind GWASs and what we have learned from GWASs for height, including how it has enhanced our understanding of the underlying biology of human growth. We also highlight the implications of GWASs in terms of prediction of adult height and our understanding of Mendelian growth disorders.

scholarly journals Synthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height

2012 ◽  
Vol 21 (23) ◽  
pp. 5193-5201 ◽  
Author(s):  
Julian C. Lui ◽  
Ola Nilsson ◽  
Yingleong Chan ◽  
Cameron D. Palmer ◽  
Anenisia C. Andrade ◽  
...  
Keyword(s):  
Growth Plate ◽  
Association Studies ◽  
Human Growth ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Expression Microarray ◽  
Novel Genes ◽  
Genome Wide

scholarly journals The Genetics of Bone Loss: Challenges and Prospects

2011 ◽  
Vol 96 (5) ◽  
pp. 1258-1268 ◽  
Author(s):  
Braxton D. Mitchell ◽  
Laura M. Yerges-Armstrong
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Mineral ◽  
Association Studies ◽  
Evidence Synthesis ◽  
Susceptibility Genes ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Mineral Density ◽  
Genome Wide

Context: A strong genetic influence on bone mineral density has been long established, and modern genotyping technologies have generated a flurry of new discoveries about the genetic determinants of bone mineral density (BMD) measured at a single time point. However, much less is known about the genetics of age-related bone loss. Identifying bone loss-related genes may provide new routes for therapeutic intervention and osteoporosis prevention. Evidence Acquisition: A review of published peer-reviewed literature on the genetics of bone loss was performed. Relevant studies were summarized, most of which were drawn from the period 1990–2010. Evidence Synthesis: Although bone loss is a challenging phenotype, available evidence supports a substantial genetic contribution. Some of the genes identified from recent genome-wide association studies of cross-sectional BMD are attractive candidate genes for bone loss, most notably genes in the nuclear factor κB and estrogen endocrine pathways. New insights into the biology of skeletal development and regulation of bone turnover have inspired new hypotheses about genetic regulation of bone loss and may provide new directions for identifying genes associated with bone loss. Conclusions: Although recent genome-wide association and candidate gene studies have begun to identify genes that influence BMD, efforts to identify susceptibility genes specific for bone loss have proceeded more slowly. Nevertheless, clues are beginning to emerge on where to look, and as population studies accumulate, there is hope that important bone loss susceptibility genes will soon be identified.

scholarly journals The Genetics of Type 2 Diabetes: A Realistic Appraisal in 2008

2008 ◽  
Vol 93 (12) ◽  
pp. 4633-4642 ◽  
Author(s):  
Jose C. Florez
Keyword(s):  
Type 2 Diabetes ◽  
Prediction Models ◽  
Association Studies ◽  
Evidence Synthesis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Major Work ◽  
Therapeutic Implications ◽  
Genome Wide

Context: Over the last few months, genome-wide association studies have contributed significantly to our understanding of the genetic architecture of type 2 diabetes. If and how this information will impact clinical practice is not yet clear. Evidence Acquisition: Primary papers reporting genome-wide association studies in type 2 diabetes or establishing a reproducible association for specific candidate genes were compiled. Further information was obtained from background articles, authoritative reviews, and relevant meeting conferences and abstracts. Evidence Synthesis: As many as 17 genetic loci have been convincingly associated with type 2 diabetes; 14 of these were not previously known, and most of them were unsuspected. The associated polymorphisms are common in populations of European descent but have modest effects on risk. These loci highlight new areas for biological exploration and allow the initiation of experiments designed to develop prediction models and test possible pharmacogenetic and other applications. Conclusions: Although substantial progress in our knowledge of the genetic basis of type 2 diabetes is taking place, these new discoveries represent but a small proportion of the genetic variation underlying the susceptibility to this disorder. Major work is still required to identify the causal variants, test their role in disease prediction and ascertain their therapeutic implications.

scholarly journals An Integrative Genomics Approach for Associating Genome-Wide Association Studies Information With Localized and Metastatic Prostate Cancer Phenotypes

2017 ◽  
Vol 12 ◽  
pp. 117727191769581 ◽  
Author(s):  
Chindo Hicks ◽  
Ritika Ramani ◽  
Oliver Sartor ◽  
Ritu Bhalla ◽  
Lucio Miele ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Susceptibility ◽  
Metastatic Prostate Cancer ◽  
Association Studies ◽  
Biological Pathways ◽  
Genome Wide Association ◽  
Molecular Networks ◽  
Genome Wide Association Studies ◽  
Disease States ◽  
Genome Wide

High-throughput genotyping has enabled discovery of genetic variants associated with an increased risk of developing prostate cancer using genome-wide association studies (GWAS). The goal of this study was to associate GWAS information of patients with primary organ–confined and metastatic prostate cancer using gene expression data and to identify molecular networks and biological pathways enriched for genetic susceptibility variants involved in the 2 disease states. The analysis revealed gene signatures for the 2 disease states and a gene signature distinguishing the 2 patient groups. In addition, the analysis revealed molecular networks and biological pathways enriched for genetic susceptibility variants. The discovered pathways include the androgen, apoptosis, and insulinlike growth factor signaling pathways. This analysis established putative functional bridges between GWAS discoveries and the biological pathways involved in primary organ–confined and metastatic prostate cancer.

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