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August 26, 2016
Digest

Tapping Crowd-Sourced Data Unearths Trove of Depression Genes

Scientists have discovered 15 genome sites—the first ever—linked to depression in people of European ancestry. Many of these regions of depression-linked genetic variation turn out to be involved in regulating gene expression and the birth of new neurons in the developing brain.

man showing signs of depression woman showing signs of depression
Scientists discovered 15 genome sites—the first ever—linked to depression.

But, in a twist, the researchers didn’t have to sequence anyone’s genes. Instead, they analyzed data already shared by people who had purchased their own genetic profiles via an online service and elected to participate in its research option. This made it possible to leverage the statistical power of a huge sample size to detect weak genetic signals associated with a diagnosis likely traceable to multiple underlying illness processes.

This novel use of crowd-sourced data was confirmed with results from traditional genetics approaches in the study, funded by NIH.

Dr. Roy Perlis of Harvard/Massachusetts General Hospital, a grantee of NIMH and NHGRI, and colleagues from industry reported on their findings Aug. 1 in the journal Nature Genetics.

It’s well known that at least some depression runs in families and some risk is inherited. Yet, prior to this study, conventional genome-wide approaches had failed to reliably identify chromosomal sites associated with the illness in populations with European roots. Since depression is thought to be like fever—a common set of symptoms likely rooted in multiple causes—lumping together genetic data from people with different underlying illness processes likely washed out, or statistically diluted, subtle evidence of effects caused by risk genes.

To increase their odds of detecting these weak genetic signals, the researchers adopted a strategy of studying much larger samples than had been used in the earlier genome-wide studies. They first analyzed common genetic variation in 75,607 people of European ancestry who self-reported being diagnosed or treated for depression and 231,747 healthy controls of similar ethnicity. These data had been shared by people who purchased their own genetic profiles via the 23 and Me web site and agreed to participate in the company’s optional research initiative, which makes data available to the scientific community while protecting privacy.

Study Supports Surgery for Myasthenia Gravis

In a global study of myasthenia gravis, an autoimmune disease that causes muscle weakness and fatigue, researchers found that surgical removal of an organ called the thymus reduced patients’ weakness and their need for immunosuppressive drugs. The study, published in the New England Journal of Medicine, was partially funded by NIH.

“Our results support the idea that thymectomy is a valid treatment option for a major form of myasthenia gravis,” said a leader of the study, Dr. Gil Wolfe of Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, New York.

The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone was a randomized, controlled study conducted on 126 patients ages 18-65 between 2006 and 2012. The researchers compared the combination of surgery and immunosuppression with the drug prednisone with prednisone treatment alone. They performed extended transsternal thymectomies on 57 patients. This major surgical procedure aims to remove most of the thymus, which requires opening of a patient’s chest.

On average, the researchers found that the combination of surgery and prednisone treatment reduced overall muscle weakness more than prednisone treatment alone. The researchers also found that patients who had surgery required lower daily doses of prednisone than the patients receiving prednisone alone.

The researchers also found that patients who had surgery required lower daily doses of prednisone than the patients receiving prednisone alone. They had less need for additional immunosuppressant drugs as well.

“This is a study that the myasthenia gravis community has needed for a long time,” said Dr. Robin Conwit, NINDS program director. “We hope it becomes a model for rigorously testing other treatment options.”

NIH Begins Testing Investigational Zika Vaccine in Humans

NIAID recently launched a clinical trial of a vaccine candidate intended to prevent Zika virus infection.
NIAID recently launched a clinical trial of a vaccine candidate intended to prevent Zika virus infection.

PHOTO: NIAID

NIAID has launched a clinical trial of a vaccine candidate intended to prevent Zika virus infection. The early stage study will evaluate the experimental vaccine’s safety and ability to generate an immune system response in participants. At least 80 healthy volunteers ages 18-35 years at 3 study sites in the United States, including the Clinical Center, are expected to participate in the trial. Scientists at NIAID’s Vaccine Research Center developed the investigational vaccine—called the NIAID Zika virus investigational DNA vaccine—earlier this year.

The study is part of the U.S. government response to the ongoing outbreak of Zika virus in the Americas. According to the Centers for Disease Control and Prevention, more than 50 countries and territories have active Zika virus transmission. In the U.S. and its territories, more than 6,400 Zika cases have been reported.

Although Zika infections are usually asymptomatic, some people experience mild illness lasting about a week. However, Zika virus infection during pregnancy can cause a serious birth defect called microcephaly, as well as other severe fetal defects of the brain and other organs. There are no vaccines or specific therapeutics to prevent or treat Zika virus disease.

The NIAID Zika virus investigational DNA vaccine approach is similar to that used for another investigational vaccine developed by NIAID for West Nile virus. That vaccine candidate was found to be safe and induced an immune response when tested in a phase 1 clinical trial.

The investigational Zika vaccine includes a small, circular piece of DNA— called a plasmid—that scientists engineered to contain genes that code for proteins of the Zika virus. When the vaccine is injected into the arm muscle, cells read the genes and make Zika virus proteins, which self-assemble into virus-like particles. The body mounts an immune response to these particles, including neutralizing antibodies and T cells. DNA vaccines do not contain infectious material—so they cannot cause a vaccinated individual to become infected with Zika—and have been shown to be safe in previous clinical trials for other diseases.

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