Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


CHOP-led study detects dozens of genes for adult height

Technique leverages gene-dense data chip for new discoveries

As much as 90 percent of variation in adult height may be caused by genetic inheritance, but a multitude of genes are involved. Most of these have yet to be discovered.

Now a new meta-analysis of data from more than 100,000 people has identified variants in over two dozen genes that were not previously associated with height. The study also confirmed genetic associations in more than 30 previously known height genes. "Although the discoveries may not have immediate clinical use, the approach we used will undoubtedly be helpful in discovering genes that influence other traits and diseases," said the co-study leader, Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia.

Using an existing gene chip customized to include approximately 50,000 SNPs (single-base changes in one letter of DNA's genetic code) in genes having a high likelihood of association with cardiovascular disease, the study team searched variants for SNPs linked to adult height. This study, said Hakonarson, which used height as a lead phenotype for a gene-rich SNP chip enhanced in rare variant coverage, suggests that such platforms will succeed in identifying genetic variants that contribute to multiple other cardiovascular diseases, and potentially to other complex traits.

"This is a proof-of-concept that more dense genotyping of selected gene-rich datasets allows us to find additional genes that have gone undetected in studies using conventional SNP arrays," said Hakonarson. Hakonarson and co-study leader Brendan J. Keating, D.Phil., also from the Center for Applied Genomics, led the large, international collaborative group whose study appeared online Dec. 30 in the American Journal of Human Genetics.

Many of the variants are in locations with interesting functional roles—in energy metabolism, growth hormones, circadian rhythm and cellular growth—of possible relevance to the biology of growth. The study team identified 64 height-associated genes, 27 of which had not been previously associated with height.

The meta-analysis included DNA from over 114,000 adults from six ethnic groups. The researchers used the IBC array, also called the CardioChip, previously designed by Keating to study genes identified or postulated to play a role in cardiovascular disease. The chip includes some 50,000 SNPs from 2,000 gene regions—about 10 percent of known human genes.

The researchers chose height as an easy-to-measure trait that is highly heritable, usually stable over adult life, and routinely recorded in large population-based studies. The CHOP scientists analyzed gene data from over 65,000 individuals, and Keating collaborated with researchers at dozens of centers throughout the world who genotyped samples from another 48,000 additional study subjects. In all, 47 studies contributed to this meta-analysis.

The specialized gene array provided very dense coverage in known and putative cardiovascular disease regions. The array's design allowed the researchers to capture richer genetic diversity from many resequencing studies and to detect SNPs with low frequency in many diverse human populations. Two of the novel uncommon SNP findings were in genes with compelling evidence of a biological role in determining height. The IL-11 gene is essential to normal bone development and the SMAD3 gene is made active by a growth factor involved with height. Many of the low-frequency SNPs, said the researchers, have strong effects, and may point the way to functional genes.

The researchers used a gene-centric approach, employing an array enriched with specific genes and avoiding non-coding sections of the genome. "The chip we used has high-density genetic coverage in a range of highly prioritized genes, and similar high-density chips may be useful in studying other complex genetic traits," said Hakonarson.

He added that "This discovery method is currently much less expensive than full-genome sequencing, which, as the technology advances, is becoming increasingly prevalent in identifying lower-frequency, disease-related genes. The near future may offer a window of opportunity for this type of technique, using large samples and dense genetic coverage, until whole-genome sequencing becomes more affordable."

Keating said that these results suggest that if the sample sizes are large enough, genotyping arrays with SNP content of less than 5 percent frequency in the population have the ability to capture new disease- and trait-associated variants that common SNP arrays have missed. These low-frequency variants also confer greater effect sizes in this study and may be a lot closer to disease causality.

"Meta-Analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height," American Journal of Human Genetics, published online Dec. 30, 2010, to publish in January 2011 print edition. doi: 10.1016/j.ajhg.2010.11.007

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 460-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit

John Ascenzi | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>