At a glance:
A team of researchers from Harvard Medical School, Brigham and Womens Hospital, Socios En Salud, and the Broad Institute at Harvard and MIT report they have identified the single largest genetic contributor to height known to date.The findings, published in Nature,are based on an analysis of samples from ethnically diverse Peruvians, a population known to have the shortest stature in the world.
The team identified a previously unknown, population-specific variant of the FBN1 gene (E1297G). The variant, found exclusively in individuals of Native American ancestry, showed a striking association with lower height.
Each copy of the gene was associated with an average of 2.2 centimeters (around 0.8 of an inch) reduction in height. People who have two copies, or two alleles, of the gene variant were, on average 4.4 centimeters (1.7 inches) shorter in stature. The effect is an order of magnitude greater than the effects that previously identified gene variants have on human heightin the range of 1 millimeter (0.04 inches).
This study dramatically highlights the advantage of studying different populations and having a diverse, worldwide strategy to understanding the human genome, said study senior author Soumya Raychaudhuri, professor of medicine and of biomedical informatics at HMS, director for the Center for Data Sciences at Brigham and Womens Hospital, and an Institute member at the Broad Institute. We learned new things about how complex genetic traits work. Our findings have implications for important diseases linked to FBN1 that we could not have learned without looking at this population.
The multi-institutional international research project brought together computational biologists, epidemiologists, community health workers, dermatologists and experts on a variety of genetic and infectious diseases, using a variety of genomic, computational and imaging techniques. The results of their collaboration shed new light on the genetics of height, a key model system for studying complex, multigene systems that are crucial for understanding wellness and disease.
A wide range of mutations in the FBN1 gene have long been known to cause Marfan syndrome, an inherited connective tissue disorder marked by hypermobility of the joints, greater height compared to ones family members and, in some instances, by cardiovascular problems.
The newly identified variant, however, is not associated with disease.
One critical insight from this study is how genetic variants in the same gene can have very different effects, said lead author Samira Asgari, HMS research fellow in medicine at Brigham and Womens. Before now, if you asked a geneticist what a variant in this gene would do, they would probably say that they cause a disease. But that's not what we found.
On the contrary, based on the researchers analysis of the distribution of E1297G variant in the Peruvian population and throughout the wider Native American population, this variant may actually confer an evolutionary advantage, the researchers said, because it appears to have been selected for by evolution.
The study found that the new variant is notably more frequent in coastal Peruvian populations than in populations from the Andes or the Amazon, which suggests that short stature might be the result of adaptation to factors that are associated with the coastal environment in Peru, the researchers said.
These findings, based on one of the few studies of the genetics of Native American populations, highlight the importance of including diverse populations in biomedical research.
It's really important to include underrepresented populations, particularly in these kinds of studies that are models for the way other multigene, complex traits function, said Megan Murray, the Ronda Stryker and William Johnston Professor of Global Health at HMS and a senior author of the study. Leaving some people out means we might miss an important part of the picture were trying to see. And any people who are left out arent likely to reap the benefits of this kind of research.
Height is a complex genetic trait, and one that is easy to measure and provides an important model system for understanding how complex genetic systems work.
Meta analyses of genetic studies of height conducted on predominately European populations include more than 700,000 individuals, the researchers noted. This research has identified about 4,000 different genetic variations known to have an impact on an individuals height. Most such variants might make a persons stature less than one millimeter taller or shorter for each copy of the variant a person has.
In comparison, this variant that we found has a 2.2 cm effect per allele, Asgari said. Thats huge for a height variant.
The new variant was not present in any of the large genetic studies conducted with European majority populations.
The genomes the team analyzed in Peru are quite distinct from those analyzed in Europe or North America. About 80 percent of the genes of an average Peruvian come from their Native American ancestry, according to previous research.
Until now, Peruvians have not been included in any genomic studies of height. by studying a small, previously overlooked population, the researchers pinpointed an allele that showed a bigger effect on height than all the other variants.
Just amassing and amassing data isnt the answer, Raychaudhuri said. If youre not looking at different populations, you're going to miss really important stuff.
The E1297G variant appears in the genomes of 5 percent in the Peruvian population, but it occurs in the genomes of less than 1 percent of people of Native American descent from Mexico. The variant is completely absent from the genome of people of European descent.
We're doing studies in populations that are not normally on the map, Raychaudhuri said. This relatively small project is the largest genetic study thats been done in Peru at this point.
The new study grew out of a series of projects led by HMS researchers in Peru, including a long-term collaboration between Murray and colleagues with the health care delivery nongovernmental organization Socios En Salud, the Peruvian affiliate of Partners In Health.
Murrays work in Peru has centered around the epidemiology and genetics of tuberculosis. Her collaboration with Raychaudhuris team includes a previous study reported in Nature Communications last year that analyzed how a given individuals genetics impact their chances of becoming infected or ill with tuberculosis and identified a gene associated with TB progression.
After completing that project, Raychaudhuri and Asgari saw an opportunity to explore what the Peruvian genome might reveal about height. When their initial work revealed that there was a relationship to Marfan, other colleagues suggested they look for skin anomalies that are characteristic of variants in FBN1. The team grew, as they brought in Esther Freeman, HMS assistant professor of dermatology, a dermatologist and an epidemiologist at Massachusetts General Hospital. Working in Lima, the team tracked down homozygous individuals to analyze their skin, and found that it tracked with what would be expected with this genetic abnormality.
These diverse skills were all crucial to the process of discovery that allowed the researchers to produce this paper, the researchers said.
If you want to do really cool science you have to get out of your corner and collaborate, Asgari said.
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
Read this article:
Worlds Shortest Population Reveal the Largest Genetic Contributor to Height - Technology Networks
- June 11th At Westport, CT: Federal Red Flags, HIPAA Security Rules and Fraud Prevention - November 7th, 2009 [November 7th, 2009]
- Do not learn Dvorak! - November 7th, 2009 [November 7th, 2009]
- You Can’t Solve Problems By Making It Illegal To Have The Problem - November 7th, 2009 [November 7th, 2009]
- A Force Fix for Healthcare - November 7th, 2009 [November 7th, 2009]
- Yahble, HIT, Bubblecon, BIZDEV!, Solid State - November 7th, 2009 [November 7th, 2009]
- 15 things that suck about the Palm Pre - November 7th, 2009 [November 7th, 2009]
- What an Indie Genomics Lab Looks Like - November 7th, 2009 [November 7th, 2009]
- Practice Fusion: Class D Felony? - February 26th, 2010 [February 26th, 2010]
- Practice Fusion Responds - March 7th, 2010 [March 7th, 2010]
- Practice Fusion: Do the math: $44,000 is a LIE - March 10th, 2010 [March 10th, 2010]
- How Much Until Doctors Approve of 23andMe? - March 10th, 2010 [March 10th, 2010]
- Biochemicals as Media, Not Methods - March 10th, 2010 [March 10th, 2010]
- More Practice Fusion Reality Distortion - March 10th, 2010 [March 10th, 2010]
- Same Test Results: 23andMe is Myriad is BRCA is Medicine - March 12th, 2010 [March 12th, 2010]
- BRCA is 23andMe is Myriad is Medicine - March 13th, 2010 [March 13th, 2010]
- Getting Serious About Genomics as Common Medical Practice - March 15th, 2010 [March 15th, 2010]
- The New John Mackey of Genetics: Linda Avey? - March 15th, 2010 [March 15th, 2010]
- Keep the Medical, Well, Medical - March 16th, 2010 [March 16th, 2010]
- If 23andMe shuts down, it won’t be for some mundane reason like the bills weren’t paid - March 16th, 2010 [March 16th, 2010]
- If I Run A Medical Practice, How Do I Use A 23andMe? - March 17th, 2010 [March 17th, 2010]
- 23andMe Contract in Bad Faith - March 19th, 2010 [March 19th, 2010]
- Doctors CANNOT Use 23andMe Due To 23andMe’s Bad Faith Contract - March 20th, 2010 [March 20th, 2010]
- Pathway Compared to 23andMe and Navigenics - March 22nd, 2010 [March 22nd, 2010]
- There’s a Word for “Views Differ” When One View Is The State - March 24th, 2010 [March 24th, 2010]
- Association for Molecular Pathology, et al. v. USPTO, et al. – Opinion - March 29th, 2010 [March 29th, 2010]
- Birth of a Super Villain - April 3rd, 2010 [April 3rd, 2010]
- “Medical Products” like 23andMe must not become the new “Financial Products” - April 4th, 2010 [April 4th, 2010]
- How I Would Apply Genomic Technology In Clinical Use Today - April 5th, 2010 [April 5th, 2010]
- Gmail Enterprise: World’s Best EMR - April 6th, 2010 [April 6th, 2010]
- Brief Primer on Health Law Compliance - April 9th, 2010 [April 9th, 2010]
- Spoiler: You ARE the “Valids” - April 9th, 2010 [April 9th, 2010]
- Rachel Lehmann-Haupt Line by Line Take Down - April 9th, 2010 [April 9th, 2010]
- Is Medicare Bankrupt? What the Hell Is Going On? - April 17th, 2010 [April 17th, 2010]
- The Big Shuffle: Medicare Cuts Rates by 21.3% (but not “technically”) - April 17th, 2010 [April 17th, 2010]
- “Tech Hiring Binge” == “Fear for Your Job, Nerds” - April 18th, 2010 [April 18th, 2010]
- How Bad is Bad? $.20 on the Private Medical Insurance Dollar - April 20th, 2010 [April 20th, 2010]
- Update: How Bad is Bad? It Used to Be $.45 on the Medical Insurance Dollar - April 20th, 2010 [April 20th, 2010]
- World’s Best “EMR” for $1000: Google Spreadsheets + iPad - April 21st, 2010 [April 21st, 2010]
- Don’t Insult Me with your “AOL Keyword” Strategy, Google Health - April 21st, 2010 [April 21st, 2010]
- How to Play LAWGAMES - April 23rd, 2010 [April 23rd, 2010]
- Top 4 Predatory Schemes Encroaching on American Medicine: Part 1 - April 25th, 2010 [April 25th, 2010]
- What’s the Big Deal About iPads? - April 27th, 2010 [April 27th, 2010]
- Got Google Android for Google I/O - April 27th, 2010 [April 27th, 2010]
- Google Enterprise meets HIPAA and HITECH Compliant Laws - April 29th, 2010 [April 29th, 2010]
- Pixels of Accuracy CHALENGE: Diagnostic Medical Imaging - April 29th, 2010 [April 29th, 2010]
- 23andMe Launder AlioGenetics Doesn’t Even Bother to Remove 23andMe Logo - April 30th, 2010 [April 30th, 2010]
- Anthem of CT Denies $600 Until “Subscriber Responds to our Coordination of Benefits Questionnaire” - May 1st, 2010 [May 1st, 2010]
- Apple And Google Team Up To Launch Revolutionary Mobile Health System - May 1st, 2010 [May 1st, 2010]
- Funny Pictures from This Year Building the Medical Practice - May 6th, 2010 [May 6th, 2010]
- Remote Medical Video Monitoring on iPad and iPhone - May 7th, 2010 [May 7th, 2010]
- Google Calendar Overhead Waiting Room Display - May 7th, 2010 [May 7th, 2010]
- Various Whiteboards on Solid State Medical Operations - May 7th, 2010 [May 7th, 2010]
- The Raw Facts about Counsyl - May 7th, 2010 [May 7th, 2010]
- Brawndo: Still Mutilating Thirst, Still Not Yet Sold at the Stop-n-Shop Pharmacy - May 9th, 2010 [May 9th, 2010]
- Video: Google Enterprise to Outsource Medical Administration - May 9th, 2010 [May 9th, 2010]
- Gattaca: “The Matrix” of Genomics - May 11th, 2010 [May 11th, 2010]
- 23andMe Now Diagnoses Fatal Tay-Sachs Disease - May 12th, 2010 [May 12th, 2010]
- Why Was Pathway Targeted for FDA Enforcement and Not 23andMe? - May 15th, 2010 [May 15th, 2010]
- John Dolan on Aging and the Horrifying Conclusion of GWAS - May 16th, 2010 [May 16th, 2010]
- Sam R. Riley Wants To Tell You About Practice Fusion - May 17th, 2010 [May 17th, 2010]
- Response to “Genomic Medicine: Lost” - May 19th, 2010 [May 19th, 2010]
- Death And Taxes: CMS to IRS - May 19th, 2010 [May 19th, 2010]
- Please Stop Antagonizing the AMA - May 26th, 2010 [May 26th, 2010]
- Dan Vorhaus, Attorney At Law, Legally Advises Medical Doctors Can Use 23andMe To Provide Medical Advice - May 28th, 2010 [May 28th, 2010]
- Singularity Summit 2010 in San Francisco to Explore Intelligence Augmentation - June 7th, 2010 [June 7th, 2010]
- OpenPCR: DNA amplification for anyone - June 10th, 2010 [June 10th, 2010]
- FDA sends letters to 5 genetic testing companies - June 11th, 2010 [June 11th, 2010]
- Amazon And The NIH Team Up To Put Human Genome In The Cloud - March 31st, 2012 [March 31st, 2012]
- ReproSource Comments on New Study Linking Infertility to Genetics - April 25th, 2012 [April 25th, 2012]
- Genetics 101 Part 1: What are genes? - Video - April 30th, 2012 [April 30th, 2012]
- Red Ice Radio - David Icke - Hour 1 - The Manipulation of Humanity - Video - April 30th, 2012 [April 30th, 2012]
- Genetics Part 5: Human Genetic Disorders - Video - April 30th, 2012 [April 30th, 2012]
- C2CAM - The Nephilim, Genetic Manipulation - April 30th, 2012 [April 30th, 2012]
- Human Nature talk with Robert Sapolsky, Gabor Mate, James Gilligan, Richard Wilkinson - Video - April 30th, 2012 [April 30th, 2012]
- Human Genetic Diseases - Video - April 30th, 2012 [April 30th, 2012]
- Alien Scientist on Genetics, Implants - April 30th, 2012 [April 30th, 2012]
- Research and Markets: Genetics, 6th Edition International Student Version Continues To Educate Today's Students for ... - May 4th, 2012 [May 4th, 2012]
- Myriad Genetics to Present at the Bank of America Merrill Lynch 2012 Health Care Conference - May 4th, 2012 [May 4th, 2012]
- Genetics may explain some people's dislike of meat - May 4th, 2012 [May 4th, 2012]
- 'Blond Genes' May Vary Around the World - May 4th, 2012 [May 4th, 2012]