What makes people different?
It sounds like a simple question. But eight decades after Arthur Morgan, then president of Antioch College in Yellow Springs, first posed the question, the answer remains as elusive as ever.
Morgan thought a longitudinal study of people from birth to adulthood would help solve the mystery, so in 1929 he contacted Samuel Fels, a Philadelphia businessman and philanthropist. Fels agreed to fund the project, and the Fels Longitudinal Study was born.
In 1977, the study became part of the Boonshoft School of Medicine, eventually finding a home in the Lifespan Health Research Center (LHRC) in the Department of Community Health. Now in its 81st year, the study is the longest continually running study of its kind in the nation. Beginning in 1929, pregnant women were recruited from the area around Yellow Springs, where the study was located. The babies born to those first mothers are now entering their ninth decade. At regular intervals throughout their lives, the participants have been meticulously measured to record growth and maturation, body composition, risk factors for cardiovascular disease, and more. Today, nearly 1,200 individuals are part of the ongoing study, and records are available for the 2,700 individuals who have been part of the study since its inception.
A complex dance
It turns out that what makes people different is a complex dance between genetics and environment. As researchers sifted through mounds of data on what makes each of us unique, they found that subtle environmental nudges during childhood can magnify genetic tendencies and have far-reaching effects on an individual decades later in life. “We can look at the history of these people,” said Richard Sherwood, Ph.D., director of the LHRC and associate professor of community health.
“We look at their childhood and early adulthood, and now look at their health as they’re turning into septuagenarians and octogenarians, and we see if we can identify precursors in early life that affect adulthood health.”
Unlike many similar studies, the Fels Study has a unique population, because it is family-based. As the study went on, relatives of the original mothers were added, which is paying dividends now that the human genome has been mapped.
“The family structure has been maintained for most of the study,” said Sherwood. “And that is allowing us to do a lot of genetic work using modern-day statistical genetic techniques.”
The 16-member team has been exploring a broad spectrum of human growth and development, from how genes regulate body fat and the associated risks for cardiovascular disease, to skeletal growth and maturation in children, to an analysis of osteoporosis risk factors—and more.
Looking at the big picture
Often when researchers decide to study the cause of a disease such as heart disease, they recruit a group of people afflicted with the condition. But that approach can be limiting. In contrast, the Fels Study gives a snapshot of the normal population.
“That actually gives us the flexibility to look at a variety of different things,” said Stefan Czerwinski, Ph.D., associate professor of community health. At Lifespan, “we’re doing craniofacial genetics, we’re doing osteoporosis, bone growth during childhood, obesity, and heart disease. All of those things are done, because we have cohorts that have not been recruited based on a single disease.”
According to Sherwood, much of the research appears to overlap.
“If you’re obese as a child, it affects growth hormone, so it can affect your growth, which is going to affect not only height, but skeletal maturation,” he said. “We think about this as one giant system with all these interrelated parts. We can start to tease out and look at the trait of interest, and also look at the co-variants that are affecting that. And then do that over the span of an individual’s lifetime.”
The growing epidemic of obesity and its effect on health has been much publicized. LHRC researchers are uniquely positioned to study the trend.
“In analyzing our obesity data, we have noticed that the latest generation, people born in the ’80s, tends to be much more obese than any of the previous generations,” said Czerwinski.
But researchers are finding it’s not just body fat that’s the problem—it’s the type of fat and where it’s located in the body. Visceral fat that envelops the organs deep in the abdomen is much more metabolically active than subcutaneous fat located throughout the body under the skin.
“If you have higher amounts of visceral fat, then you’re likely to have a whole cascade of effects that include increased inflammation, increased effects on lipid metabolism, and accumulation of fat in your liver, all of which leads to metabolic syndrome and risk for diabetes and heart disease,” said Czerwinski.
One common measure of visceral fat is waist circumference, but Czerwinski and his colleagues have shown that’s not always a reliable indicator.
“Over the last few years, we have developed a protocol to actually quantify the amount of fat in the viscera using MRI and separating the subcutaneous adipose tissue apart from the visceral adipose tissue,” Czerwinski said.
With this method, they have found that people with the same waist circumference can have vastly different amounts of fat stored in the viscera. “Heights and weights are good, they’re growth indicators,” Czerwinski said, “but these more refined measurements are better at being able to predict later risk.”
The genetics of osteoporosis
Scientists have long known that osteoporosis has a strong genetic component. The LHRC researchers want to determine which specific genes play a role in bone loss.
“We’re actually measuring people from 18 all the way up into their 90s,” Czerwinski said, “just to try to identify the determinants —the genes that are related to bone mineral density or peak bone mineral density.”
Several genes have been identified that have very small effects.
“They’re very common, but their effects are very minute,” said Czerwinski. “What we understand now is basically that it’s polygenic, in that there are many, many genes that contribute to osteoporosis risk.”
Bone tissue is continuously being formed and reabsorbed, and genes control each of those processes. As an individual ages, absorption outpaces formation, and bone loss occurs.
“Ultimately, we want to identify the pathways that are important, and to be able to deliver gene products that can counteract excessive loss later in life,” Czerwinski said.
Secular trends raise more questions
With more than 80 years of data to study, LHRC researchers have noted many secular trends, or changes in a characteristic or disease trait over time.
“This gets to the value of the longitudinal studies, because over the course of our study, blood pressure measures went down, and now they’re on their way back up,” Sherwood said. “Generally you think of a secular trend as a shift up or down, but here you’ve got a U-shaped trend, which you can only identify with good longitudinal data. It becomes a really interesting question to ask, ‘Why is that?’
“A lot of our business is identifying the questions to be asked,” he said. In the end, finding the answer to Arthur Morgan’s question may lie in knowing what questions to ask. VS
For more information, visit med.wright. edu/lhrc