The odds of acquiring a disease are often portrayed as a tug of war between two foes: genes and environment. The battle is not always evenly matched. A disease such as cystic fibrosis is entirely genetic – if a child inherits the mutated CFTR gene from both parents, no environment will prevent the condition. On the other hand, environment can trump genetics for many other diseases, such as the relationship between exposure to the toxic substance arsenic and the cancer mesothelioma. But in most places, the tug of war is a more balanced contest, with the genetic factors controlling risk competing with a range of environmental factors from diet and exercise to education and climate.
Scientists have traditionally kept score on these competitions using a measure called heritability, the percentage of a phenotype (a disease or characteristic) that is determined by genetic factors. One way to measure heritability is with twin studies, which assemble data from thousands of pairs of identical or fraternal twins as a natural experiment of whether genes or environment win out. But a new study from University of Chicago psychiatry researchers shows that the blanket term of “environment” does not have to mean things outside the body – it can also refer to the biological state inside the body.
For the paper, published last month in Behavioral Genetics, a team led by post-doc Terrie Vasilopoulos set out to test the relationship between two health conditions: hypertension and cognitive decline. Previous research examining this link established hypertension as a risk factor for the loss of cognitive ability late in life, producing decreases in performance similar to those seen in Alzheimer’s disease and other forms of dementia. Meanwhile, heritability research revealed that genetics play a large part in a person’s risk of cognitive decline in their golden years. So does the “internal environment” of hypertension – and whether it is treated – move the tug-of-war of heritability for cognitive issues toward genes or environment?
To test this hypothesis, the team used data from the Vietnam Era Twin Study of Aging – over 1,200 male-male twin pairs who served in the military between 1965 and 1975. With an age range between 51 and 60, the researchers looked at an important time in a man’s cognitive lifetime before the first signs of dementia typically set in, Vasilopoulos said.
“We really think we are capturing a very important developmental period with the guys that we’re studying, especially for cognitive phenotypes,” said Vasilopoulos, a researcher in the laboratory of Kristen Jacobson, assistant professor of psychiatry. “The groundwork for these bad things that are happening to you later in life are being laid when you’re much younger. By finding these mechanisms early in life, we can start to figure out better game plans of trying to protect people and help people make smarter choices when younger so we don’t see these bad effects when they’re older.”
The men were divided into three groups: those with hypertension receiving treatment, those with untreated hypertension, and those without hypertension. On overall measures of cognitive ability, the three groups showed no differences in performance, suggesting that the researchers were indeed looking at an age before any noticeable decline begins. But when the heritability of different cognitive measures was examined, a relationship with hypertension and anti-hypertension medication emerged.
For two measures – episodic memory and visual-spatial ability – the heritability of how a person performed on the tests actually decreased in those with untreated hypertension, relative to the other two groups. That is, in men with high blood pressure not taking medication, the “internal environment” of the disease outweighed the influence of genetics on two early warning signs of cognitive problems.
“These are the two types of cognitive domains that are first affected by age-related cognitive decline,” Vasilopoulos said. “In Alzheimer’s disease or other types of neurodegeneration or just regular aging, those are the most affected or first affected. So we really think we are honing in on the mechanisms of why hypertension is bad for cognitive performance late in life.”
On the other side, men with high blood pressure taking medication were similar to men without hypertension on the heritability of cognitive performance, even when their blood pressure remained high enough to qualify for hypertension. So it’s possible that a secondary effect of anti-hypertension medication – increasing cerebral blood flow or preventing brain lesions – preserved a person’s genetic background as superior for determining cognitive ability.
Changes in heritability over a person’s lifetime have been studied before, though most focus on critical periods during childhood when an environment can outweigh genes. The researchers said that the new results suggest that critical periods may also exist later in life, when a person’s health and other factors might dampen or amplify the effect of genes.
“There’s a certain amount of time when you’re younger when you might be able to alter genetic programming, but does it have lasting effects?,” Jacobson said. “So what we’re trying to do now in an aging sample is go to the other end of life: what are the things that are really important as you get older when it comes to cognitive function.”
As the twins of the VETSA sample continue to be tracked as they move from mid-life to senior citizenship, changes in cognitive performance can continue to be tracked and measured against hypertension and medication use. However, Vasilopoulos also hopes to look for more diseases or conditions that fall on the environment side of the tug-of-war in determining mental health at advanced ages.
“As you get older, health-related issues are much more important to biological and especially cognitive development,” Vasilopoulos said. “We really have to take a multi-pronged approach when you’re looking at cognitive health over time. Mental health and psychosocial health might be the most important things to your cognition, while education or early life experiences might have less of an impact on the genes and environment underlying cognition.”
Vasilopoulos T, Kremen WS, Kim K, Panizzon MS, Stein PK, Xian H, Grant MD, Lyons MJ, Toomey R, Eaves LJ, Franz CE, & Jacobson KC (2011). Untreated Hypertension Decreases Heritability of Cognition in Late Middle Age. Behavior genetics PMID: 21688193