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Prenatal choices are just the start
Prenatal choices are just the start
alpha press
THIS WEEK
The effects of lifestyle decisions on our health are being teased out more accurately than ever Debora MacKenzie
are more likely to have a higher IQ, and this is passed to the child, obscuring any effect of drinking. Such traits are called confounders. You can correct for them, or try to make them equal in both groups, so the women being compared differ only in their drinking habits – but shared traits that you are unaware of can still cloud the results. “All epidemiological studies are confounded somehow,” says epidemiologist David Batty at University College London. The answer, says Ron Gray at the University of Oxford, a coauthor of the new study, is to use genes as a proxy for drinking. For example, the gene for alcohol dehydrogenase (ADH), an enzyme that breaks down alcohol, can contain small mutations called singlenucleotide polymorphisms (SNPs). These slow the enzyme’s action. Humans carry several dehydrogenase genes and differ in the number of SNPs that they contain – from none to 10. The more of these mutations that a fetus has, the more slowly
WHAT makes us unhealthy? Sometimes the answer is easy. In 1854 an English doctor, John Snow, founded modern epidemiology by mapping a cholera outbreak in London and noticing that sick people lived near one public water pump. In the now classic version of the story, he had the pump’s handle removed and the outbreak ended. Often, though, the true links between sickness and environmental exposures are more subtle. Now, a novel method promises a revolution to rival Snow’s, by using our knowledge of human genes to pinpoint how the environment and our lifestyle choices affect health. Last week, the method burst into the public arena, with the finding that moderate drinking during pregnancy lowers the future IQ of a developing fetus (PLoS One, doi.org/jrg). Previous studies that charted mothers’ drinking and children’s IQs have given conflicting results. That’s because they use classic epidemiology, which involves surveying a large group of women “The true links between sickness and our who drink during pregnancy and environmental exposures another similar group who don’t, are very subtle” then comparing their kids’ IQs. Sounds simple, but what if it will break down the alcohol that mothers who drink have other its mother drinks. So if alcohol traits in common that nonreduces IQ, the IQ should be lower drinkers don’t have, and it is one in children with more mutations, or more of those traits, rather and that in turn should be than the alcohol, that actually independent of social or other influences IQ? In fact, it turns variables. When Gray and his out that women who drink colleagues studied these moderately during pregnancy 8 | NewScientist | 24 November 2012
mutations in the children of more than 4000 mothers, those who had four or more of the SNPs averaged 3.5 IQ points lower on a standard test than children with 2 SNPs or fewer – but that was only the case if their mothers drank 1 to 6 units per week during the pregnancy (see “What do a few IQ points mean?”, right). Genes made no difference to IQ if the mothers did not drink. “This avoids confounders, and shows it must be alcohol that is making the difference,” says Gray. Alcohol is just the start. George Davey Smith at the University of Bristol, UK, and colleagues proposed in 2003 that epidemiologists might find genes that affect the extent of
your exposure to environmental and dietary chemicals, or affect your own fatness or blood-sugar level. If so, those genetic variants could then be used as a proxy for the exposure itself in assessing how it leads to disease. The method is called Mendelian randomisation (MR). Genes inherited randomly, according to Mendel’s laws, are also inherited independently of other things that affect the disease in question – i.e. confounders. Davey Smith’s group found that having one or another mutation in 5000 genes that affect the extent of your exposure to potential causes of disease bares no relation to many confounding factors, such as your social class,
In this section n Extreme recycling turns manure into food, page 10 n Higgs offers no clues to exotic physics, page 12 n Chips that mimic the human brain, page 21
The technique is starting to clear up all sorts of conflicted epidemiology. For years, people thought raising high-density lipoprotein – commonly known as “good cholesterol” – would protect from heart attack, says Davey Smith. But a large trial of a drug that raises good cholesterol,
“Now we know that moderate alcohol during pregnancy does affect IQ, why risk it?”
What do a few iq points mean? “Research is showing that even small differences in IQ correlate with socio-economic achievement,” says Ron Gray at the University of Oxford, who last week showed that moderate drinking in pregnancy can reduce the future IQ of a developing fetus. The study doesn’t show how much higher IQs would be if no alcohol was consumed, only that faster rather than slower breakdown of alcohol prevented 3.5 points worth of damage. The total damage is unlikely to be very much greater, says Gray. How might this influence a child’s future? Studies that attempt to tease out the effect of IQ on health struggle with confounders (see main
story). But Ian Deary at the University of Edinburgh, UK, says that in studies that account for this, 15 more IQ points made young people 24 per cent less likely to die in the next 20 years, and 14 per cent less likely to develop high blood pressure, obesity and diabetes. The effect is about the same size as the impact of smoking on the same diseases, and doesn’t appear to be influenced by social class. So what effect might that glass of champagne during a second trimester have had? “There’s no way we could determine whether such a low dose has an effect,” says Gray. “But now we know moderate alcohol does affect IQ. If you have a choice, why risk it?”
published this month, saw no such benefit. MR could have saved the expense: a study in August of 15 genes that affect cholesterol metabolism found that people with SNPs causing low or high levels of good cholesterol have the same heart attack risk. This suggests there was some confounder in the traditional epidemiological studies that concluded good cholesterol lowered the risk of heart attack. Another big question is also on its way to being answered: how is being fat bad for you? The FTO gene makes a protein associated with obesity and fat mass. It predisposes a person to obesity and accounts for some of the variations in fatness –Make an informed decision– between people. Along with 30 more genetic proxies for obesity, say, or whether you eat cheese. it could reveal how being In other words, studies of overweight influences diseases obesity’s links to disease can be such as cancer. confounded by obese individuals’ The next phase, says Davey tendency to also drink and smoke, Smith, is to use MR to sort but using a specific gene mutation through thousands of chemical linked to obesity instead of obesity markers in the “metabolome” – itself means the mutation’s effect all the chemical intermediates in on a disease should reveal the a metabolic process, which can impact of obesity on that disease, now be identified. How genetic and nothing else. And now, variants change those, and studies of human DNA have also affect disease, should show revealed useful mutations to which metabolic processes focus on. “In 2003 MR was cause disease. hypothetical,” says Davey Smith. The point, he says, is not to “Now, it’s going mainstream.” show how genes cause disease, For the first time, the American which was the hope of our early Society for Human Genetics efforts to study human DNA. annual conference included a “It is to use genes to show session on MR at its meeting what parts of our behaviour in San Francisco this month. or environment make us ill.” n 24 November 2012 | NewScientist | 9
alpha press
THIS WEEK
The effects of lifestyle decisions on our health are being teased out more accurately than ever Debora MacKenzie
are more likely to have a higher IQ, and this is passed to the child, obscuring any effect of drinking. Such traits are called confounders. You can correct for them, or try to make them equal in both groups, so the women being compared differ only in their drinking habits – but shared traits that you are unaware of can still cloud the results. “All epidemiological studies are confounded somehow,” says epidemiologist David Batty at University College London. The answer, says Ron Gray at the University of Oxford, a coauthor of the new study, is to use genes as a proxy for drinking. For example, the gene for alcohol dehydrogenase (ADH), an enzyme that breaks down alcohol, can contain small mutations called singlenucleotide polymorphisms (SNPs). These slow the enzyme’s action. Humans carry several dehydrogenase genes and differ in the number of SNPs that they contain – from none to 10. The more of these mutations that a fetus has, the more slowly
WHAT makes us unhealthy? Sometimes the answer is easy. In 1854 an English doctor, John Snow, founded modern epidemiology by mapping a cholera outbreak in London and noticing that sick people lived near one public water pump. In the now classic version of the story, he had the pump’s handle removed and the outbreak ended. Often, though, the true links between sickness and environmental exposures are more subtle. Now, a novel method promises a revolution to rival Snow’s, by using our knowledge of human genes to pinpoint how the environment and our lifestyle choices affect health. Last week, the method burst into the public arena, with the finding that moderate drinking during pregnancy lowers the future IQ of a developing fetus (PLoS One, doi.org/jrg). Previous studies that charted mothers’ drinking and children’s IQs have given conflicting results. That’s because they use classic epidemiology, which involves surveying a large group of women “The true links between sickness and our who drink during pregnancy and environmental exposures another similar group who don’t, are very subtle” then comparing their kids’ IQs. Sounds simple, but what if it will break down the alcohol that mothers who drink have other its mother drinks. So if alcohol traits in common that nonreduces IQ, the IQ should be lower drinkers don’t have, and it is one in children with more mutations, or more of those traits, rather and that in turn should be than the alcohol, that actually independent of social or other influences IQ? In fact, it turns variables. When Gray and his out that women who drink colleagues studied these moderately during pregnancy 8 | NewScientist | 24 November 2012
mutations in the children of more than 4000 mothers, those who had four or more of the SNPs averaged 3.5 IQ points lower on a standard test than children with 2 SNPs or fewer – but that was only the case if their mothers drank 1 to 6 units per week during the pregnancy (see “What do a few IQ points mean?”, right). Genes made no difference to IQ if the mothers did not drink. “This avoids confounders, and shows it must be alcohol that is making the difference,” says Gray. Alcohol is just the start. George Davey Smith at the University of Bristol, UK, and colleagues proposed in 2003 that epidemiologists might find genes that affect the extent of
your exposure to environmental and dietary chemicals, or affect your own fatness or blood-sugar level. If so, those genetic variants could then be used as a proxy for the exposure itself in assessing how it leads to disease. The method is called Mendelian randomisation (MR). Genes inherited randomly, according to Mendel’s laws, are also inherited independently of other things that affect the disease in question – i.e. confounders. Davey Smith’s group found that having one or another mutation in 5000 genes that affect the extent of your exposure to potential causes of disease bares no relation to many confounding factors, such as your social class,
In this section n Extreme recycling turns manure into food, page 10 n Higgs offers no clues to exotic physics, page 12 n Chips that mimic the human brain, page 21
The technique is starting to clear up all sorts of conflicted epidemiology. For years, people thought raising high-density lipoprotein – commonly known as “good cholesterol” – would protect from heart attack, says Davey Smith. But a large trial of a drug that raises good cholesterol,
“Now we know that moderate alcohol during pregnancy does affect IQ, why risk it?”
What do a few iq points mean? “Research is showing that even small differences in IQ correlate with socio-economic achievement,” says Ron Gray at the University of Oxford, who last week showed that moderate drinking in pregnancy can reduce the future IQ of a developing fetus. The study doesn’t show how much higher IQs would be if no alcohol was consumed, only that faster rather than slower breakdown of alcohol prevented 3.5 points worth of damage. The total damage is unlikely to be very much greater, says Gray. How might this influence a child’s future? Studies that attempt to tease out the effect of IQ on health struggle with confounders (see main
story). But Ian Deary at the University of Edinburgh, UK, says that in studies that account for this, 15 more IQ points made young people 24 per cent less likely to die in the next 20 years, and 14 per cent less likely to develop high blood pressure, obesity and diabetes. The effect is about the same size as the impact of smoking on the same diseases, and doesn’t appear to be influenced by social class. So what effect might that glass of champagne during a second trimester have had? “There’s no way we could determine whether such a low dose has an effect,” says Gray. “But now we know moderate alcohol does affect IQ. If you have a choice, why risk it?”
published this month, saw no such benefit. MR could have saved the expense: a study in August of 15 genes that affect cholesterol metabolism found that people with SNPs causing low or high levels of good cholesterol have the same heart attack risk. This suggests there was some confounder in the traditional epidemiological studies that concluded good cholesterol lowered the risk of heart attack. Another big question is also on its way to being answered: how is being fat bad for you? The FTO gene makes a protein associated with obesity and fat mass. It predisposes a person to obesity and accounts for some of the variations in fatness –Make an informed decision– between people. Along with 30 more genetic proxies for obesity, say, or whether you eat cheese. it could reveal how being In other words, studies of overweight influences diseases obesity’s links to disease can be such as cancer. confounded by obese individuals’ The next phase, says Davey tendency to also drink and smoke, Smith, is to use MR to sort but using a specific gene mutation through thousands of chemical linked to obesity instead of obesity markers in the “metabolome” – itself means the mutation’s effect all the chemical intermediates in on a disease should reveal the a metabolic process, which can impact of obesity on that disease, now be identified. How genetic and nothing else. And now, variants change those, and studies of human DNA have also affect disease, should show revealed useful mutations to which metabolic processes focus on. “In 2003 MR was cause disease. hypothetical,” says Davey Smith. The point, he says, is not to “Now, it’s going mainstream.” show how genes cause disease, For the first time, the American which was the hope of our early Society for Human Genetics efforts to study human DNA. annual conference included a “It is to use genes to show session on MR at its meeting what parts of our behaviour in San Francisco this month. or environment make us ill.” n 24 November 2012 | NewScientist | 9