Win Zaw Oo, 36, poses for a photo with his family ahead of his medical check-up at a clinic in Yangon June 30, 2013. Win Zaw Oo, who stands at 7 feet 5 inches tall, is Myanmar's tallest man, according to his medical team. 
 
 WASHINGTON It's no secret that if your dad is tall and your mother is tall, you are probably going to be tall. But fully understanding the genetics of height has been a big order for scientists. 
 
 Researchers on Sunday unveiled what they called the biggest such study to date, analyzing genome data from more than a quarter million people to identify nearly 700 genetic variants and more than 400 genome regions relating to height. 
 
 How tall or short a person becomes is estimated to be 80 percent genetic, with nutrition and other environmental factors accounting for the rest. The world's people on average have become taller over the past few generations because of factors including improved nutrition. 
 
 "We study height for two main reasons," said Dr. Joel Hirschhorn, a geneticist and pediatric endocrinologist at Boston Children's Hospital and the Broad Institute of Massachusetts Institute of Technology and Harvard University. 
 
 "For over 100 years, it's been a great model for studying the genetics of diseases like obesity, diabetes, asthma that are also caused by the combined influence of many genes acting together. So by understanding how the genetics of height works, we can understand how the genetics of human disease works," he said. 
 
 In addition, short stature in childhood is a major clinical issue for pediatric endocrinologists. Knowing genes and their variants that are important for height eventually may help doctors diagnose children who have a single major underlying cause for short stature, Hirschhorn added. 
 
 The international team of researchers analyzed data from the genomes of 253,288 people of European ancestry, all from Europe, North America and Australia. They perused about 2 million common genetic variants in these individuals and identified 697 gene variants in 424 gene regions as related to height. 
 
 Many genes pinpointed in the study, published in the journal Nature Genetics, are probably important regulators of skeletal growth, but were not previously known to be involved, the researchers said. 
 
 Some were related to collagen, a component of bone; a component of cartilage called chondroitin sulfate; and growth plates, the area of growing tissue near the ends of the body's long bones. 
 
 The researchers said there is much more to learn. 
 
 "We've found the genetic variants - the pieces of DNA that vary from person to person - that account for 20 percent of the genetic component to normal variation in height," said geneticist Timothy Frayling of Britain's University of Exeter. 
 
 "This compares to a situation in 2007 when we knew absolutely nothing about the genes and regions of the human genome involved in normal height differences despite everyone knowing height is very strongly genetic." 
 
 The team's previous 2010 study involved a smaller number of people and identified 199 genetic variants residing in 180 genome regions. 
 
 "By doubling the sample size, we doubled the number of gene regions that are connected to height, and greatly increased by about seven-fold the number of actual genes where we can make a connection to the biology of normal skeletal growth," Hirschhorn said. 
 
 (Reporting by Will Dunham; editing by Susan Thomas) ||||| The largest genome-wide association study (GWAS) to date, involving more than 300 institutions and more than 250,000 subjects, roughly doubles the number of known gene regions influencing height to more than 400. The study, from the international Genetic Investigation of Anthropometric Traits (GIANT) Consortium, provides a better glimpse at the biology of height and offers a model for investigating traits and diseases caused by many common gene changes acting together. Findings were published online October 5 by Nature Genetics. 
 
 "Height is almost completely determined by genetics, but our earlier studies were only able to explain about 10 percent of this genetic influence," says Joel Hirschhorn, MD, PhD, of Boston Children's Hospital and the Broad Institute of MIT and Harvard, leader of the GIANT Consortium and co-senior investigator on the study. "Now, by doubling the number of people in our study, we have a much more complete picture of how common genetic variants affect height--how many of them there are and how much they contribute." 
 
 The GIANT investigators, numbering in the hundreds, shared and analyzed data from the genomes of 253,288 people. They checked about two million common genetic variants (those that showed up in at least 5 percent of their subjects). From this pool, they pinned down 697 (in 424 gene regions) as being related to height, the largest number to date associated with any trait or disease. 
 
 "We can now explain about 20 percent of the heritability of height, up from about 12 percent where we were before," says co-first author Tonu Esko, PhD, of Boston Children's Hospital, the Broad Institute and the University of Tartu (Estonia). 
 
 "The study also narrows down the genomic regions that contain a substantial proportion of remaining variation--to be discovered with even larger sample sizes," adds co-senior investigator Peter Visscher, PhD, of the University of Queensland, Australia. 
 
 Greater size, greater power 
 
 Height is a model trait for understanding how human genetics works--especially for traits produced by not one gene, but many. Height is easy to measure, and an estimated 80 percent of variation in height is genetic. 
 
 Previous large-scale genome-wide association studies (GWAS) have indicated that a large number of genes influence height, and suggested that the majority of heritability comes from common genetic variants, not rare ones. Because sample sizes have not been large enough to draw definitive conclusions, the GIANT team built the largest sample to date. 
 
 "When you double the sample size and increase your statistical power, you can make new discoveries," says Hirschhorn. "Our results prioritize many genes and pathways as important in skeletal growth during childhood. Without a highly collaborative model, there's no way we could get this work done." 
 
 The researchers believe their results answer critics of population-scale GWAS, who have argued that increasing the sample size yields diminishing returns or results that become meaningless. 
 
 "In 2007 we published the first paper that identified the first common height gene, and we have now identified nearly 700 genetic variants that are involved in determining height," says co-senior investigator Timothy Frayling, PhD, of the University of Exeter, U.K. "We believe that large genetic studies could yield similarly rich lists in a variety of other traits." 
 
 The biology of height 
 
 Many of the 697 height-related genetic variants were located near genes known to be involved in growth, but there were also plenty of surprises. 
 
 "There were some pathways that we knew were important, but had not come out in previous GWAS," says Hirschhorn, who is also an endocrinologist at Boston Children's. "Many of the genes we identified are likely to be important regulators of skeletal growth, but were not known to be involved until now. Some may also be responsible for unexplained syndromes of abnormal skeletal growth in children. As you increase the sample size, you get more biology." 
 
 For example, the mTOR gene is well known to be involved in cellular growth, but had not previously been connected with human skeletal growth. Other genes confirmed as important include genes involved in metabolism of collagen (a component of bone) and chondroitin sulfate (a component of cartilage), as well as networks of genes active in growth plates, the area of growing tissue near the ends of the long bones. Still other genes point to biology whose relationship with height isn't yet known. 
 
 Among GIANT's future goals is to look at variants that occur at lower than 5 percent frequency, and to look for variants in the non-protein-coding portions of genes. 
 
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 In addition to Wood and Esko, the study's co-first authors were Sailaja Vedantam and Tune Pers, PhD, Boston Children's Hospital/Broad Institute; Jian Yang, PhD, University of Queensland (Brisbane, Australia) and Stefan Gustafsson, PhD, Uppsala University (Uppsala, Sweden). The study's numerous funding sources included the March of Dimes and grants from the National Institutes of Health and many other countries. 
 
 About Boston Children's Hospital 
 
 Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including seven members of the National Academy of Sciences, 14 members of the Institute of Medicine and 14 members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 395-bed comprehensive center for pediatric and adolescent health care. Boston Children's is also the primary pediatric teaching affiliate of Harvard Medical School. 
 
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 About the Broad Institute of MIT and Harvard 
 
 The Eli and Edythe L. Broad Institute of MIT and Harvard was launched in 2004 to empower this generation of creative scientists to transform medicine. The Broad Institute seeks to describe all the molecular components of life and their connections; discover the molecular basis of major human diseases; develop effective new approaches to diagnostics and therapeutics; and disseminate discoveries, tools, methods, and data openly to the entire scientific community.
– Scientists are knee-deep in a freakishly large study (part of the aptly named GIANT Consortium) to better understand the genetics at play in human height. They tell Reuters that height can tell us a lot about various aspects of human health—including diseases like "obesity, diabetes, asthma that are also caused by the combined influence of many genes acting together," says one geneticist—with taller height often being linked to better health, and shorter stature in children to worse health. The study involved more than 250,000 participants, all of European ancestry, and focused on 2 million common genetic variants (meaning they appeared in at least 5% of their subjects). From those, they identified 697 gene variants in 424 regions related to height—which is the largest number ever associated with a trait or disease, according to the group's press release. In spite of the scope of their findings, the researchers say they're just getting started. "We can now explain about 20% of the heritability of height, up from about 12% where we were before," says a study co-author. That might not seem like a lot, but it's a giant step forward. "In 2007... we knew absolutely nothing about the genes and regions of the human genome," adds one geneticist. (Meanwhile, the tallest dog in the world recently died at the age of 5.)