Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world among people over 60. The two forms of the disease – wet and dry – both cause vision loss by destroying cells in the central portion of the retina.

In the last few years, progress in understanding AMD has been made thanks in part to the discovery of several common genetic variants, or SNPs, that together explain a large part of the risk for the disease. Several of these recently discovered AMD SNP associations have pointed to a role for the immune system in the disease.

A new study published online Monday in The Lancet yet again links the immune system to AMD. As is the case for several of the previously found SNPs, the variant found in this study is in a gene involved in the complement pathway, an arm of the immune system that facilitates the elimination of both pathogens and cellular debris.

Many years ago some researchers suspected that the complement system might be involved in AMD. Proteins from this pathway were found in drusen, the small crystalline deposits that build up in the eyes of people with AMD. But it was not until genetic studies started to show a link between AMD and complement genes that other scientists began to sit up and take notice.

In two separate samples — one British with 479 AMD patients and 479 controls, the other from the U.S. with 248 cases and 252 controls — Ennis et al found that the odds of developing AMD were reduced for every A T a person had at SNP rs2511989. Those with one A T had 0.68 times the odds of people with the GG CC genotype, and people with two As Ts had 0.44 times the odds.

(23andMe customers can check their data for rs2511989 using the Browse Raw Data feature. Note: The original post talked about As and Gs.  But our Browse Raw Data actually gives the data in terms of Ts and Cs.  Two different ways of looking at the same thing!  Sorry for the confusion!)

SNP rs2511989 is in the SERPING1 gene, which encodes a protein that regulates the complement pathway.

“Our findings add to the growing understanding of the genetics of age-related macular degeneration, which should ultimately lead to novel treatments for this common and devastating disease,” the authors write.

In an accompanying comment in The Lancet, Caroline Klaver and Arthur Bergen, two scientists not associated with the research, said the results of Ennis et al need to be replicated in large, independent samples before SERPING1 will be established as a true risk factor for AMD. They also suggest that the researchers may find other SNPs within the gene that are even more tightly linked to AMD.

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Meet Marcela, a product manager at 23andMe. A product manager represents the customer’s needs while also considering engineering constraints and business requirements. Her most recent projects were focused on building the user experience of those who participate in research through 23andWe and helping to build the burgeoning 23andMe community.

Marcela on the 23andMe Service:

“I was born in South America, but both my mother’s and my father’s ancestors came from Japan. I found it unsurprising to learn that my paternal haplogroup was one that is only found in Japan today, and that one-third of the Japanese population can trace its paternal ancestry to the people who first arrived in Japan, crossing an ancient land bridge that no longer exists. (A woman has the same paternal haplogroup as her father, her brother, or any male in her father’s line. I learned mine by sharing genomes with my father!) However unsurprising it was, though, I was delighted to learn that this piece of history was preserved throughout all the recent migrations in my family. At the same time, I find it fascinating how long-ago migrations are represented in our genetics — through haplogroups and their predicted migrations or the details in Ancestry Paintings, such as the one shown for the sample Uyghur woman.”

“I’m also really passionate about 23andWe. Right now, people think of genetics as a blueprint, as an answer to the question, ‘What are my chances of having a certain trait?’ However, research in genetics is telling us so much more than that now.”

“It’s helping scientists understand more about the pathways involved in certain diseases and it’s leading to changes in health care and treatments. For example, understanding the genetics behind Age-related Macular Degeneration (AMD) caused scientists to start looking at the condition as an immune disorder.”

“Even research on some of the less serious traits on our site can turn out to be extremely valuable — researchers can study traits that are present in a large percentage of the population to learn about the basic mechanisms behind more rare conditions. The work of some scientists studying the photic sneeze (sneezing in the sunlight) could lead to insights into the biology of epilepsy. Studies of caffeine metabolism might lead to greater insights into other, more complicated drug pathways.”

“Another aspect of genetics research is helping us understand who we are and why we are that way. How did culture and biology interact to make some populations lactose intolerant and others not? What other details in human history and migrations will research in genetics uncover? Why is it that 90% of the population (including me) is right-handed? Genetics may answer only a few of these questions, but I’d be amazed to learn those few answers.“

Marcela on being a 23andMe employee:

“I studied Human Biology and Computer Science, and my honors thesis dealt with privacy in genetic databanks. I never imagined that I would find a job that combines my interests in product management, consumer internet software, and genetics.”

“I love the challenges at work. I want to design the experience of using our site so that my parents can easily understand the wealth and detail of genetic information we provide. We balance many different considerations in our site. Privacy is always our primary concern, but we also want people to learn from friends and family members. We want to make scientific studies accessible, but without losing the important details. We provide such a new type of information that we’re constantly building and rebuilding features based on the many perspectives in the 23andMe team and the many pieces of feedback our users send.”

Think you’d like to join the team? Check out our jobs page!

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A new treatment for one type of age-related macular degeneration that is currently in clinical trials may have an unintended consequence: it could cause another form of the disease.

Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the western world among people over 60. The two forms of the disease – wet and dry –both cause vision loss by destroying cells in the central portion of the retina.

In the last few years, progress in understanding AMD has been made thanks in part to the discovery of several SNPs linked to both forms of the disease. Yesterday a report published online in the New England Journal of Medicine described yet another AMD SNP association, this time specific for the dry form of the disease.

The SNP, rs3775291, is in the gene for toll-like receptor 3 (TLR3), a protein that helps the immune system fight off viruses.

“What TLR3 does in the case of infection is sacrifice an infected cell to protect the neighborhood,” said the study’s senior author Kang Zhang in a statement.

Lab tests in human eye cells and genetically engineered mice found that the T version of the SNP decreases TLR3’s cell killing potential by reducing its activation in response to viral cues. Studies of patients and controls found that version of the SNP also decreases the risk of developing dry AMD.

“This discovery has significant implications for diagnosing the dry form of AMD, which is the most prevalent form. It also allows us to develop new drugs to the treat the dry form of AMD, for which there is currently no treatment,” Zhang said.

Jayakrishna Ambati, another author of the study, plans to start clinical trials testing the effectiveness of TLR3 inhibitors in patients at risk for developing dry AMD next year.

The discovery of the role of TLR3 activation in dry AMD may have come just in time. Several drugs for the treatment of wet AMD currently in clinical trials may actually trigger the protein, thus treating one form of the disease while causing the other.

The new treatments for wet AMD are based on a general method called RNA interference (RNAi) that uses short RNA molecules to interrupt genes. In wet AMD, the goal is to disrupt genes involved in the aberrant blood vessel growth seen in the eyes of patients.

Research from Ambati’s lab published earlier this year, however, found that RNAi treatments (regardless of their target), activate TLR3. The immune protein confuses the RNA molecules with the genetic material of viruses, its sworn enemies.

People with the protective T version of rs3775291 might still be good candidates for RNAi treatments for wet AMD. Their TLR3 proteins are naturally less reactive. But for the 43% of people of European ancestry with two copies of the more active C version of the SNP, these treatments could do more harm than good.

“Ironically, in some individuals, using RNAi to cure wet AMD might actually increase the risk for blindness from dry AMD,” Zhang said.

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