Tag Archives: genetics

By Karene Booker
Reprinted from Cornell Chronicle, May 29, 2014

A screen shot from the BRCA Gist (Web-tutor) video tutorial that is designed to help explain the incidence of breast cancer in people with the BRCA mutations.

A screen shot from the BRCA Gist (Web-tutor) video tutorial that is designed to help explain the incidence of breast cancer in people with the BRCA mutations.

About one in eight American women will be diagnosed with breast cancer during her lifetime – more than 200,000 this year alone. A simple blood test can determine if a woman faces increased risk due to genetic mutations, yet decisions about whether to get the test and what to do about the results are far from simple – a fact exemplified by Angelina Jolie’s choice to undergo a double mastectomy last year upon learning she carried a harmful BRCA1 gene mutation.

To help women grappling with these decisions, Cornell psychologist Valerie Reyna and colleagues developed a computer-based system using artificial intelligence to mimic one-on-one human tutoring.

“To our knowledge, this is the first use of an Intelligent Tutoring System (ITS) in patients’ medical decision making,” said Reyna, professor of human development and director of the Human Neuroscience Institute in Cornell’s College of Human Ecology.

The breast cancer Web-tutor, called BRCA Gist (Breast Cancer Genetics Intelligent Semantic Tutoring), is more effective in helping women understand breast cancer risk and their options than traditional educational materials, reports a study published online May 14 in Medical Decision Making ahead of print.

BRCA Gist provides customized instruction on breast cancer and how it spreads, risk factors, genetic mutation testing and the consequences of testing using an animated talking avatar that engages women in “dialogue” about breast cancer and can even answer women’s questions.

The Web-tutor draws on well-vetted, publically available information and expert advice from physicians, “but the crucial added ingredient,” said Reyna, “is that it effectively conveys the bottom-line or gist of the information.” And that’s what people rely on to make medical decisions, not detailed facts, she said. The key to the Web-tutor’s success, she added, is its basis in fuzzy-trace theory, a model of memory and decision-making that she developed.

To test the Web-tutor’s effectiveness, the researchers conducted two randomized-control trials involving more than 400 women. The studies measured knowledge gains and decisions about genetic testing after completing the new Web-based tutorial, viewing the comparable information from the National Cancer Institute (NCI) website or completing an unrelated Web-based curriculum.

The team found that those who participated in the Web-tutor scored higher on knowledge of breast cancer, genetic testing and genetic risk than those using the NCI website, and both groups scored higher than the control group. In making judgments about genetic testing for those with no risk, the Web-tutor helped participants understand that most women do not have known genetic risks and are not good testing candidates, the authors say. Their results support the concept that a gist-based intervention powered by artificial intelligence can be an effective tool to aid patients’ medical decision-making, they concluded.

The study, “Efficacy of a Web-based Intelligent Tutoring System for Communicating Genetic Risk of Breast Cancer,” was supported by the National Cancer Institute and the National Institutes of Health. The co-authors are Christopher Wolfe, Colin Widmer, Elizabeth Cedillos, Christopher Fisher and Audrey Weill of Miami University of Ohio, and Cornell graduate student Priscila Brust-Renck.

Karene Booker is an extension support specialist in the Department of Human Development.

Related Links:
Valerie Reyna
The Paper

By Susan S. Lang
Reprinted from the Cornell Chronicle, March 3, 2014

Mendle

Mendle

The age at which people become sexually active is genetically influenced – but not when they grow up in stressful, low-income household environments, reports a new study.

“Our study shows that environmental influences – rather than genetic propensities – are more important in predicting age at first sex (AFS) for adolescents from stressful backgrounds, who have few societal and economic resources,” says Jane Mendle, assistant professor of human development in the College of Human Ecology, pointing out that genes determine when teens begin puberty, which is a strong predictor of AFS.

“In fact, genes contribute only negligibly to AFS for these teens. It can almost be thought of as the environment ‘taking over’ the natural developmental trajectory that might occur in a less stressful background,” she adds.

For teens from financially advantaged backgrounds, on the other hand, the environment is much less influential and genes play a more important role in predicting AFS, Mendle notes.

The study, co-authored with University of Texas at Austin researchers, was published online in January in the journal Developmental Psychology.

While many studies have examined either genetic influences or environmental influences on AFS, “ours was one of the very first to consider gene-environment interactions in AFS, or how genetic expression may vary according to environmental circumstances,” Mendle says.

Using a sample of 1,244 pairs of identical twins (who share 100 percent of their genes) and non-twin full siblings (who share 50 percent of their genes) from the National Longitudinal Study of Adolescent Health, the researchers found that genetic influences on AFS were suppressed among low-socioeconomic-status and ethnic-minority teens compared with higher socioeconomic status and ethnic-majority youth. Father absence did not uniquely moderate genetic influences on AFS.

“And because we looked at identical twins and siblings, we could account for the importance of big family differences – and that enabled us to focus solely on understanding the environmental influences in AFS,” she says.

In addition to genetic influences, the use of twins and siblings in the study design accounted for shared environmental influences, such as religion or certain aspects of parenting, for siblings in the same family and for environmental influences that were unique to each youth.

Their findings “are broadly consistent with previous findings that genetic influences are minimized among individuals whose environments are characterized by elevated risk,” the researchers wrote.

“There has been a lot of dialogue and controversy in America on how to handle adolescent sexuality, and what programs may be most effective in reducing some of the outcomes associated with high-risk sexual behavior in teens,” Mendle says. “Many factors predict whether a teen is sexually active and when he or she transitions to sexual maturity. Our results help us understand in what contexts these factors will be malleable.”

The study, “Early Adverse Environments and Genetic Influences on Age at First Sex: Evidence for Gene x Environment Interaction,” co-authored by Texas researchers Marie D. Carlson and K. Paige Harden, received no outside funding.

Related Information

By H. Roger Segelken
Reprinted from Cornell Chronicle October 30, 2013
Anderson 110x150

Anderson

Some people are genetically predisposed to see the world darkly, according to a study from the laboratory of a researcher now on the faculty of Cornell’s College of Human Ecology.

Adam K. Anderson, associate professor of human development, is continuing his research on emotions, genetics and perception, which began at his laboratory at the University of Toronto in collaboration with scientists at the University of British Columbia (UBC). Their study, published in September in Psychological Science, found a previously known gene variant causing some individuals to perceive emotional events – especially negative ones – more acutely than others.

“This genetic variation contributes to how emotions bias individuals to see the same world in different ways,” says Anderson. “More than just how we may later remember, these findings suggest genetics influence how our brains pick and choose which events to perceive in the first place.”

The gene in question is the ADRA2b deletion variant, which influences the neurotransmitter norepinephrine. Previously found to play a role in the formation of emotional memories, the new study shows that the ADRA2b deletion variant also plays a role in real-time perception.

Some 200 study participants were shown positive, negative and neutral words in a rapid succession, each at 1/10th of a second. While all individuals perceived positive words better than neutral words, participants with the ADRA2b gene variant were more likely to perceive negative words than others.

“These individuals may be more likely to pick out angry faces in a crowd of people,” says Rebecca M. Todd of UBC’s Department of Psychology. “Outdoors, they might notice potential hazards – places you could slip, loose rocks that might fall – instead of seeing the natural beauty.”

The findings shed new light on ways in which genetics – combined with other factors such as education, culture and moods – can affect individual differences in emotional perception and human subjectivity, the researchers say.

Future work on this topic in Anderson’s laboratory intends to examine whether individuals with these very same genetic variants, depending on their environment and stage of development, can be coaxed to enhance perception of the positive rather than the negative.

The study, “Genes for Emotion-Enhanced Remembering Are Linked to Enhanced Perceiving,” was funded in part by the Canadian Institutes of Health Research.

By Susan Kelley
Reprinted from Cornell Chronicle, February 11, 2013

Valerie Reyna

Reyna

Charles Brainerd

Brainerd

Defying the widely held belief that a specific gene is the biggest risk factor for Alzheimer's disease, two Cornell developmental psychologists and their colleagues report that people with that gene are more likely to develop mild cognitive impairment -- but not Alzheimer's.

The study suggests that older adults with healthy brain function can get genetic tests to predict increased risk of future mild cognitive impairment. However, once they are impaired cognitively, the tests won't predict their likelihood of developing Alzheimer's.

"Right now, genetic tests are used in exactly the opposite way. That is, healthy people don't get the tests to predict their risk of mild cognitive impairment, but impaired people get them to predict their risk of Alzheimer's disease," said Charles Brainerd, professor of human development and the study's lead co-author with Valerie Reyna, professor of human development. "So, impaired people think that tests will tell them if they are at increased risk of Alzheimer's, which they won't. And healthy people think that tests won't tell them whether they are at increased risk of cognitive impairment, which they will."

The researchers describe their findings in the January issue of Neuropsychology (27:1).

The work builds on previous research by Brainerd and associates that suggested the ε4 allele of the APOE genotype increases the risk of mild cognitive impairment as well as Alzheimer's.

The researchers analyzed data from the only nationally representative dataset of its kind, the National Institute on Aging's Aging, Demographics and Memory Study. They looked at data from 418 people over age 70 to see if those who carried the allele were more likely to develop mild cognitive impairment compared with those who did not have the allele. They also looked at whether ε4 carriers with mild cognitive impairment were more likely to develop Alzheimer's disease compared with non-carriers with mild cognitive impairment.

They found that healthy ε4 carriers were nearly three times -- 58 percent -- more likely to develop mild cognitive impairment compared with non-carriers. However, ε4 carriers with mild cognitive impairment developed Alzheimer's at the same rate as non-carriers.

While previous studies showed that the ε4 allele was more common in people with Alzheimer's disease, this study shows that it does not increase the risk that healthy or impaired people will become demented. Rather, ε4 increases the risk that healthy people will become cognitively impaired, and impaired people are the primary source of new Alzheimer's diagnoses, Brainerd explained. "The reason ε4 is a risk factor for mild cognitive impairment, but not for progression from mild cognitive impairment to Alzheimer's disease, is that this allele is a marker of initial cognitive declines -- for example, memory and executive function -- that are associated with mild cognitive impairment but not of subsequent declines in cognition or in daily functioning that are associated with forms of Alzheimer's disease."

Brainerd also noted that the effects of ε4 in healthy adults can be detected by the mid-20s. While ε4 is not a risk factor for the severe cognitive declines that signal dementia, it is risk factor for the weaker declines that eventually produce mild cognitive impairment.

The co-authors of the paper are Ronald Petersen and Glenn Smith of the Mayo Clinic; Anna Kenney '11, Caroline Gross '12 and Emily Taub '10 of Cornell -- all of whom helped conduct the research as undergraduates in Brainerd's lab; Brenda Plassman of Duke University Medical Center; and Gwenith Fisher of the University of Michigan.

The research was supported in part by the National Institutes of Health.

By Ted Boscia
Reprinted from Cornell Chronicle, December 4, 2012

Mendle

Mendle

Teens who date and are sexually active are known to be at elevated risk for depression, but why those associations exist is poorly understood.

Now a new Cornell study has found that casual sexual "hookups" increased a teenager's odds for clinical-level depression nearly threefold, whereas dating and sexual activity within a committed relationship had no significant impact. The effects held true for boys and girls, though younger teens (13-15 years old) who had so-called "nonromantic sex" faced substantially greater risks for depression. In contrast, dating alone was not linked to depressive symptoms, nor was sexual activity within a stable, committed relationship.

Researchers led by Jane Mendle, assistant professor of human development in Cornell's College of Human Ecology, said the study provides evidence that "context is key" when trying to understand how teen relationships and sex affect their well-being. The research is published online in the Journal of Abnormal Psychology.

"Many historical and media perspectives have presented adolescent sexuality as an indicator of problematic or even socially deviant behavior," Mendle said. "But this study and other recent findings are showing that's not the case, and adolescent dating and sexuality can be viewed as normal developmental behavior."

Using a novel behavioral genetics approach that compares siblings growing up in the same home, Mendle and her co-authors analyzed responses from 1,551 sibling pairs ages 13-18 from the National Longitudinal Study of Adolescent Health, a nationally representative sample of U.S. high school students initiated in the mid-1990s. Among other topics, teens answered questions about their mental health and dating and sexual history. Nearly two-thirds of the sample's youth had dated, and two-thirds were virgins.

By comparing siblings in their study, the authors could control for family and environmental influences that might also raise one's risk for depression.

"We designed the study to give us a purer way to isolate many of the factors that could be contributing to depression," Mendle said. "It allows us to compare specific types of social activities -- in this case, dating and romantic and nonromantic sex -- to see their overall effect."

The paper notes that not all the associations at play can be unraveled, however. For instance, some teens who have depressive symptoms or clinical depression may be more likely to engage in casual sexual behaviors.

Mendle, a licensed clinical psychologist who studies how such developmental processes as puberty and sexual maturation influence teens' emotional growth, believes adolescent sexuality is important to study because it is closely tied to how well people transition into adulthood.

"One of the hallmarks of adolescence is the formation of romantic relationships, and we know that what happens in adolescence is strongly related to your psychological, physical and financial well-being for years to come," Mendle said. "Findings like this can help shape the dialogue and public debate about how to best support teen sexual health, psychological development and other areas."

The study co-authors include Sarah Moore, a Cornell graduate student in the field of human development; Joseph Ferrero, formerly a graduate student at the University of Oregon; and Paige Harden, assistant professor of psychology at the University of Texas.

The study was funded in part by Cornell.

Ted Boscia is assistant director of communications for the College of Human Ecology.

By Karene Booker
Reprinted from Cornell Chronicle, February 20, 2012

Depue

Depue

Personality disorders could be more effectively diagnosed by identifying and targeting the disrupted neurobiological systems where the disorders originate, report Cornell researchers.

The way that these mental illnesses are now classified -- based on particular patterns of thought and behavior -- is misguided and has little hard evidence to support it, reports Cornell neuroscientist Richard Depue and his colleague in a special issue of the Journal of International Review of Psychiatry (23:3).

"The behavioral features used to diagnose personality disorders do not coalesce into coherent disorders in any research," says Depue, professor of human development in the College of Human Ecology, who co-authored the article with graduate student Yu Fu. "As currently defined, the different personality disorders have overlapping behavioral symptoms that also merge imperceptibly with normal behavior. A diagnosis should define a coherent behavioral pattern and predict a particular course, prognosis and treatment. No personality disorder diagnosis can do that."

Their findings fly in the face of current medical practice. Nearly one in 10 Americans suffers from a personality disorder, a group of disabling conditions characterized by serious, sometimes catastrophic, problems with relationships and work. Behavioral features can vary widely, from pervasive disregard for the law and the rights of others (antisocial personality disorder) to extreme mood instability (borderline personality disorder).

The researchers drew their conclusions by conducting a detailed review of the brain systems that underlie the major human personality traits.

Humans have about six major personality traits, each with its own neurobiological foundation that influences such behaviors as how anxious or impulsive we are, Depue notes. For example, the underlying systems and associated personality traits in their model include anxiety/stress-reactivity (thought to underlie neuroticism and negative emotionality) and neural constraint (thought to underlie conscientiousness), among others. The variety of behaviors associated with personality disorders arise from the influence of an individual's genetic make-up and environment on neurobiological functioning, they say.

In their multidimensional model, a person's personality traits can be plotted in three-dimensional space where the axes represent the underlying neurobehavioral systems. The patterns of behavior associated with personality disorders emerge from the interaction of extremely high or low values or levels of normal traits; such extremes lead to impaired interactions, they say.

"Our model links personality traits with the underlying neurobiology, which provides a better framework for understanding how and why personality disorders develop and how they can be treated," he says. "It allows us to better predict interventions, such as certain drugs and/or environmental interventions, which may be of benefit. We can also start thinking of treatments that modify multiple neurobiological variables, rather than just one or two."

And recent discoveries in neuroscience point to the important role environment plays, particularly during early childhood, in how genes are expressed, Depue says. "So, risks for personality disorders can be either magnified or reduced by the interaction of the individual's circumstances with their genetic make-up, in a process called epigenetics. We see evidence for this in personality disorders, which are much more prevalent in those who have suffered from a variety of childhood stresses and abuse."

Their theoretical analysis has implications for the criteria used for classifying personality disorders in the Diagnostic and Statistical Manual of Mental Disorders. It also contributes to a growing body of evidence that calls for a rethinking of the approach to classifying these illnesses, based on the underlying biochemical and neural processes that result in the symptoms.

The research was supported by a grant from the National Institute of Mental Health.

Karene Booker is an extension support specialist in the Department of Human Development.

By John McKain
Reprinted from Cornell Chronicle, July 18, 2011
Charles Brainerd

Brainerd

Valerie Reyna

Reyna

Cornell scientists have shown a significant correlation for the first time between a human gene and people's risk for mild cognitive impairment (MCI), often a precursor to Alzheimer's disease and related forms of dementia.

The findings could help doctors to recommend simple preventative measures for at-risk patients, including healthy diet, exercise and intellectual activity -- all of which could forestall and even prevent chronic symptoms associated with the disease, said lead author Charles Brainerd and Valerie Reyna, professors of human development in Cornell's College of Human Ecology.

The professors, with researchers at the Mayo Clinic in Rochester, Minn., linked the ε4 allele of the apolipoprotein E (APOE) genotype to a greater likelihood of the onset of MCI in the July 4 issue of the journal Neuropsychology.

"We're excited about these findings, because they help identify the segment of the population who will most benefit from effective treatments to prevent Alzheimer's-type dementia," Brainerd said.

The clinical applications of linking this genetic marker with MCI are far-reaching, Brainerd said, because genetic testing can now be added to the neuropsychological tests that are currently the only way to identify MCI.

"What is at stake is whether genetic testing is useful for determining MCI susceptibility and candidacy for treatments that are designed to prevent or forestall/treat MCI (and therefore prevent Alzheimer's dementia)," the authors write. "If not, neuropsychological testing remains the only reliable means of identification."

Prior studies have been inconclusive owing to limits of their subject populations. In the new study, the researchers identified the link between the ε4 allele and the risk of MCI by analyzing a large data set from the National Institute on Aging, the Health and Retirement Study (HRS), that accurately represents older adults from all regions and racial and ethnic groups in the United States.

Classifying subtypes of MCI was also critical to the study's success. Led by Dr. Ronald C. Petersen and Glenn E. Smith at the Mayo Clinic, the authors successfully identified subtypes of MCI, only one of which is the precondition for Alzheimer's. The paper outlines how criteria for the different MCI subtypes developed by the Mayo researchers helped control for errors that have plagued previous studies that have attempted to identify an ε4-MCI link.

By sorting the HRS subjects who have the ε4 gene into subtypes of impairment identified in Petersen's and Smith's work, the Cornell researchers were able to show a significant correlation the ε4 gene and risk of the Alzheimer's precondition, known as amnestic MCI (or a-MCI). The results specifically show that 32 percent of study subjects who had been diagnosed as a-MCI were carriers of the ε4 APOE biomarker, as compared to only 20 percent of study subjects who had been diagnosed as normal and healthy.

The Cornell part of the research was supported by the National Institutes of Health.

John McKain is assistant dean for communications in the College of Human Ecology.

Related Links:
College of Human Ecology
Charles Brainerd
Valerie Reyna