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Tuesday, May 16, 2017

WHAT IS HERITABILITY, REALLY?

The calculated "heritability" for having two hands is essentially zero.
Image: Wikimedia Commons/Leon Brocard
In the May issue of Scientific American, I critique the latest efforts to find genetic variants that provide elevated risk for schizophrenia, the most debilitating of all mental illnesses. The story is behind a paywall, although I hope that readers will be able to get access to it either through personal or institutional subscriptions. I did, however, provide a synopsis of the main points in an interview with John Batchelor, which is available on his podcast feed.

The article included a sidebar about the heritability of schizophrenia, and some common misunderstandings about what heritability actually is. Lack of space made it impossible to go into much detail, but below I provide an expanded version of the text which includes some additional details. I hope readers will find it useful.

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Researchers have been searching for schizophrenia related genes for at least 50 years. What makes them think they will find them?  The rationale is spelled out in the introduction to nearly every scientific paper on schizophrenia genetics: The disorder has a high “heritability.” This term is often interpreted—by many researchers and the general public alike—as a measure of the relative role played by genes. Heritability is usually expressed as a percentage between zero and 100%.

Scientists have estimated the heritability of schizophrenia using several approaches, including studies of twins, both identical and fraternal. One oft cited study dates to 2003, when a research team  reported  a “meta-analysis” of 12 previous twin studies.  (In a meta-analysis, the data from earlier studies are pooled to increase statistical power.) The team concluded that schizophrenia had a heritability of 81%.

However, many researchers argue that heritability estimates for schizophrenia and other so-called complex human traits (ranging from disease susceptibility to how tall a person is) can be very misleading. One major debate  is over key assumptions used to simplify the method. One assumption is that genes and the environment do not interact but have only an additive effect; another is that genes  act independently rather than in concert. Still another, called the equal environment assumption (EEA), considers both identical and fraternal twins to be subject to the same environmental influences. Thus if identical twins are more similar than fraternals for a particular trait, that greater similarity must be entirely due to genes. But critics argue that the EEA is violated in a number of ways, including the greater likelihood that identical twins will be treated the same by their parents while they are growing up.

“These basic assumptions are wrong,” says Roar Fosse, a neuroscientist at the Vestre Viken Hospital Trust in Norway, who led a critical assessment of the EEA published in 2015. But twin researchers have mounted a vigorous defense of the approach, countering that even if the EEA and other assumptions are oversimplifications, the methodology is basically sound. “I don’t think it’s likely that current heritability numbers are substantially overestimated,” says Kenneth Kendler, a psychiatrist at Virginia Commonwealth University’s School of Medicine.

But some researchers have an even more profound critique of heritability. They argue that it is not truly an indication of the relative role of genes and environment. The actual definition of the term, they point out, is much more technical:  Heritability measures how much the variation of a trait in a particular population—whether height, IQ, or being diagnosed with schizophrenia--is due to genetic variation among the individuals in that population. “Heritability and genetic cause are not the same,” says Mary-Claire King, a geneticist at the University of Seattle. Peter Visscher, a geneticist at the University of Queensland in Australia, agrees. “It is a misconception that a high heritability implies genetic determination. Human height has a heritability of 80%, and yet environmental factors such as childhood nutrition and healthcare can have a big effect on adult height.”

As an example of how misleading heritability estimates can be, Eric Turkheimer, a behavioral geneticist at the University of Virginia, points to the human trait of having two arms. Nearly everyone in a given population has two of them, and there is normally no difference in the number of arms between identical twins—who share 100% of their genes—and fraternal twins, who are assumed to share 50% of their genes. Thus when heritability for arm number is calculated, it comes out to zero. And yet we know that having two arms is almost entirely genetically determined.


Figuring out what heritability for schizophrenia actually means is key, researchers say, because even the most high-powered genetic studies have only identified about a third of the predicted genetic component. A similar predicament faces researchers working on other complex diseases, including diabetes and Crohn’s disease, where an even higher percentage of the heritability remains unaccounted for. Will this so-called “missing heritability” eventually show up in more sophisticated studies—or will it turn out that genes are not playing as big a role as heritability estimates have long predicted? The jury is still out.

Friday, May 12, 2017

RussiaGate is exciting, but don't let it distract from organizing


The revelations of the past week are dramatic and exciting for those who really want to get at the truth about what happened during the 2016 election. Nevertheless, they could have a down side.

My main concern is that some anti-Trump people might be staking too much on evidence turning up of direct collusion between his campaign people (Manafort et al) and the Russians to influence the election. It's one thing for them to have been in touch with the Russians, and it's another thing for the Russians to have "hacked" the election, but the Russians might have been too smart (they are much smarter than Trump and his boys) to leave any traces that this was coordinated. In fact it didn't need to be, the Russians just could have been working all the angles. 

I'm not saying this is the way it was, but if it turns out that way then the investigations are going to fizzle and the Trumpists will be able to claim there was never anything serious there. It's all fine to be focused on it as long as it does not distract from the need to build a mass movement that will have impact on the streets, and in the voting booth late next year (that's still a long way off.)

Unfortunately, too many Democrats hate doing anything that might involve actually changing anybody's mind about political questions. Instead most establishment Demos prefer to slosh donor money around, build machines, and focus on voter turnout, rather than influence political views. The "return" of Hillary Clinton to political life is a bad sign that way--she represents the very worst of Democratic Party machine politics.

Sunday, April 9, 2017

Syria, Trump, Clinton, political footballs, and morality

Out of frustration with current discussions about Syria and Trump's bombing of the air field the other day, I posted this comment on the Facebook page of a good friend and colleague. I am reposting it here, for what it is worth. If it ends without clear suggestions about what to do, at least I am no worse off than anyone else talking about the war in Syria right now.


The problem I am having in the current discussion is that Syria has become a political football for all sides and persuasions. This is happening on a number of different levels. Liberals are quick to jump on Trump's use of force, but Hillary Clinton has long argued for military intervention in Syria and argued for taking out Assad's airfields and air force just hours before Trump's minimalist attack on the one air base. But I actually saw a woman Tweet that we needed a woman president who would not be so aggressive! Then there is the inconvenient fact that according to UN estimates about 400,000 Syrians have died in the war and millions are refugees. The latter consequence actually gets more attention these days than the former, but both are awful; and yet absolutely no one, anywhere, has done anything about it nor even advocated doing anything about it in most cases. Clearly negotiations have failed and they will continue to fail. After Trump's action the other day a lot of people started talking about violations of international law, not getting permission from Congress, etc etc, but actually the most serious violations of international law are those committed by Assad every time he bombs civilians--the use of chemical weapons is a very very small part of the problem. Where does all this leave us? In my own view, ONLY those who argue about Syria from a STRICTLY moral point of view have any credibility on the issue. Any other perspective is playing politics, no matter what political viewpoint is being played.

Tuesday, January 10, 2017

Smithsonian mammalogist Kris Helgen, falsely accused but now exonerated of research misconduct, leaves for Australia

Helgen leading his expedition on Mt. Kenya
Note: This post will be continually edited as new information and comment become available. Latest development is a story in the Washington Post about the resolution of the case, which kindly credits my original reporting in The Verge.

Kris Helgen, whose long battle to clear his name of accusations made by his superiors at the Smithsonian's National Museum of Natural History has finally succeeded, is leaving the museum for a new position at the University of Adelaide. Although he managed to hold onto his job after an investigation I conducted for The Verge showed that the charges and their investigation were deeply flawed, sources at the museum indicate that NMNH officials continued to make his life miserable over the past months. They stripped him of his curatorial responsibilities, isolated him from colleagues, and left him with little hope of regaining the prestige and respect he had previously enjoyed.

In an email yesterday to museum staff (see below), Helgen stated that he would start at Adelaide in March, with the rank of professor of biological sciences, a clear promotion from his current position. Helgen also stated that his "record had been cleared and efforts to fire or suspend me have been rescinded." This includes the two week suspension that NMNH director Kirk Johnson had slapped on him last fall--a serious blemish on the record of a federal employee, had it been allowed to stand.

Museum officials declined to comment on the circumstances of Helgen's departure, simply stating that the NMNH does not comment on personnel matters. However, one museum scientist familiar with the situation told me that it was the result of a settlement between museum officials and Helgen negotiated over the past period of time: "It's infuriating to me that institutional leaders would let [Johnson] unilaterally destroy [Helgen's] professional reputation and create a hostile workplace."

Don Wilson, an emeritus mammalogist at the museum and Helgen's predecessor as curator of mammals, told me that "The Smithsonian has lost one of its best and brightest. Kris will be making major contributions to science for decades to come." One of those contributions comes this week, as Helgen joins an international team to announce a new species of gibbon in the American Journal of Primatology.

Helgen will move to Adelaide with his wife, who is Australian, and their young son. Below is his message to his colleagues at the museum; I will update this report as more details come in.

From: Helgen, Kristofer M.
Sent: Monday, January 09, 2017 4:03 PM
To: NMNH-All-Users
Cc: ....
Subject: farewell
Friends
It is with excitement and sadness that I announce that I am leaving NMNH for a position in Australia. I will be taking on the role of Professor of Biological Sciences at the University of Adelaide, starting in March. My last day will be January 19. The University of Adelaide is my alma mater and my work in zoology will continue there, apace. Lauren (my wife), who has worked in Entomology and Vertebrate Zoology here at NMNH, also bids you farewell. Lauren is from Adelaide, and we will return to be with family there. We will be going home.
2016 has been challenging. Many of you learned in the press that NMNH tried to fire me over complaints related to permissions for our 2015 Roosevelt Expedition to Kenya. I am very relieved to say that my record has been cleared and efforts to fire or to suspend me have been rescinded. Thank you to so many of you for standing by me during a very hard 15 months.
I believe that the Smithsonian, especially the NMNH, is one of our greatest national assets, and I know that you all serve this institution with pride. I have been humbled to hold a Smithsonian badge for 17 years, starting as an undergraduate intern, progressing to graduate, pre-doctoral, and postdoctoral fellowships, and finally serving as a curator over the past decade. From our scientific and collections staff and fellows, to our education and exhibits teams, to all the dedicated building and custodial staff who make this museum operate in all the real and practical ways, to the remarkable officers who keep us safe, this place has felt like a family to me as much as a workplace. 
Thank you for allowing me this farewell. I hope to see all of you on regular return visits. And come and see us in Australia—our email addresses are listed above.
With best wishes for 2017 (see attached) and all else that is ahead, yours most truly,
kmh
Kris, Lauren, and Daniel Oldfield Helgen