tag:blogger.com,1999:blog-1812431336777691886.post7983022480065799726..comments2024-02-29T03:57:00.088-05:00Comments on The Mermaid's Tale: Coffee - a guilt-free pleasure?Anne Buchananhttp://www.blogger.com/profile/09212151396672651221noreply@blogger.comBlogger27125tag:blogger.com,1999:blog-1812431336777691886.post-71774757206407495122015-05-23T14:57:18.347-04:002015-05-23T14:57:18.347-04:00These are old, and legitimate arguments for the ad...These are old, and legitimate arguments for the additive components of complex traits. But they first of all state the approximate additivity, and this does in now way vitiate the likelihood that among many of the pairwise (or more-wise) interactions at the molecular and cellular level that things are additive. <br /><br />Secondly, the idea that evolution favors additivity is that the interactive effects can be transmitted if they are at a single locus, for example, because only one allele, not the combination, is transmitted to an offspring, breaking up the interaction effect. But the same sort of thing is true for complex multilocus traits even for additive combinations, and if the alleles are common enough (because they're good enough fitness-wise), then the good combinations will be common in the population. This applies, with its own dynamics, whether the effects are additive or include important aspects of interactions. <br /><br />Some have argued for the importance of epistasis because they want to wave away the problem of 'missing' heritability. That argument hasn't convinced very many people so far, I think, and even the advocates of the view basically concede that testing for epistasis is devilishly hard in practice.<br /><br />All complex analytic studies, like the twin study, are meta-analyses and make all sorts of assumptions, including about LD patterns, and interpretations hang on assumptions to a considerable extent--even if, overall, nobody can deny the importance of additive effects or their relative ease of detection in heritability studies.<br /><br />Others note that at the actual molecular level, there is no reason for pure additivity. Evolution screens on (1) luck, where additivity is irrelevant, and (2) selection which for reasons your link points out, which are not at all newly discovered!, make evolutionary sense. The central issue is the extent to which any of this makes traits predictable from genotypes. The answer is that will be partly so, depending on the genotype, and the extent to which they are so is not fixed or predictable. There is also no prior theory for the degree to which environment and genes interact additively. To some degree they will, to some approximation they will, but in any given instance they may or may not.<br /><br />But there is no need to argue about whether the methods such as are used are detecting additive effects in the statistical estimation sense. They give collective pictures of the role of genes under particular circumstances.<br /><br />Now, this is taking things far enough, because it is a case advocacy that never ends, whatever your motives are. So you should start your own blog and explain your point of view fully. We have to move on.Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-2050652805198595982015-05-23T14:42:16.506-04:002015-05-23T14:42:16.506-04:00There isn't going to be a single explanation f...There isn't going to be a single explanation for all traits. Some will be due to gene X environment interaction, some gene X gene interaction, some essentially single gene, some primarily environment (though even then of course genes are involved) and so on. So, the insistence that the additive model is the right one is just wrong. It might explain some traits. It certainly won't explain them all. Anne Buchananhttps://www.blogger.com/profile/09212151396672651221noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-44611013183233300852015-05-23T09:27:44.797-04:002015-05-23T09:27:44.797-04:00Here's a defense of the additive model I agree...Here's a defense of the additive model I agree with. If I have not articulated my view properly, this is it:<br /><br />http://infoproc.blogspot.ca/2015/05/fifty-years-of-twin-studies.html<br /><br />I don't know why you'd disagree with it.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-63530631303007251262015-05-22T17:35:25.199-04:002015-05-22T17:35:25.199-04:00Sure, but are you disagreeing with my reading of V...Sure, but are you disagreeing with my reading of Visscher's paper and that meta-analysis, or with the papers themselves? That's what I'd like to know, because I do not understand what the disagreement is exactly.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-46656080582883529182015-05-22T09:21:42.514-04:002015-05-22T09:21:42.514-04:00Anonymous,
I think it's time for us to agree ...Anonymous,<br /><br />I think it's time for us to agree to disagree. Anne Buchananhttps://www.blogger.com/profile/09212151396672651221noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-88644436435450853332015-05-22T00:49:46.788-04:002015-05-22T00:49:46.788-04:00It seems to me, Prof. Buchanan, that those who rai...It seems to me, Prof. Buchanan, that those who rail against additive effects are doing so on the basis of ideology.<br /><br />Visscher demonstrated that in this paper, I think it's clear the importance of additive effects:<br /><br />http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000008Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-19003595612869394382015-05-21T10:15:19.541-04:002015-05-21T10:15:19.541-04:00Anonymous,
It behooves the reader of a scientific...Anonymous,<br /><br />It behooves the reader of a scientific paper to think, first, about how it might be wrong. Words like "vindicated" and "incontrovertibly" suggest that's not your approach. Science should not be ideology.<br /><br />Anne Buchananhttps://www.blogger.com/profile/09212151396672651221noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-82092325305722492872015-05-21T06:11:49.143-04:002015-05-21T06:11:49.143-04:00From my reading of the paper, twin resemblance for...From my reading of the paper, twin resemblance for a majority (69%) of traits appears to be solely due to additive genetic variation. This vindicates Visscher's and Plomin's work into finding the genetic instatntiation by assuming the additive model for the heritability of traits, which is incontrovertibly "there" considering the decades of twin studies.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-58694570025634217432015-05-20T06:24:29.237-04:002015-05-20T06:24:29.237-04:00Thanks for pointing out this new paper, which we h...Thanks for pointing out this new paper, which we had not seen if it was even online when we wrote this post. There are a mix of semantic, epistemological, and conceptual issues here.<br /><br />Of course everything is 'genetic' in many fundamental ways. That environment is important cannot be denied, and there are shared aspects not all of which can be adequately accounted for. And the molecular way that genes (and other functional genomic elements) work is inherently by interaction; there is no reason to think that genetic variation is all additive at the actual molecular level. There are many issues here, too many for a response to a Comment.<br /><br />If the coffee responses are genetic as you note, but also complex, to the extent that people are mainly different in their genetic aspects of the trait, then saying that the trait is 'genetic' may be true but at the same time rather misleading or even useless.<br />Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-5153496505743620442015-05-20T05:25:33.383-04:002015-05-20T05:25:33.383-04:00The individual's reaction to coffee and long-t...The individual's reaction to coffee and long-term effects is probably genetically variable, and heritable. <br /><br />Like what this meta-analysis of twin studies tells us; non-additive effects of genes and shared environment matters very little. For all traits, actually.<br /><br />Massive meta-analysis of twin studies: The shared environment and non-additive genetic variation have little impact.<br /> https://infotomb.com/6z8qy.pdf<br />Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-76607885525411032402015-05-14T21:19:58.565-04:002015-05-14T21:19:58.565-04:00Geoff
We need thoughtful people...like you...to wr...Geoff<br />We need thoughtful people...like you...to wrestle with the problem, rather than just caving in to 'normal science' (as Kuhn put it), which is what statistical epidemiology and genetics are largely about these days. I hope you've found a tolerant, thoughtful advisor!Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-82744698963616412792015-05-14T21:05:31.878-04:002015-05-14T21:05:31.878-04:00I don't know that the way things work in epide...I don't know that the way things work in epidemiology is terribly different, Ken. Someone comes up with an animal study suggesting exposure X is carcinogenic. Another group does a case-control study. Someone else does a cohort study. Group #4 tries to find a situation where X has been withdrawn or increased in a community due to quasi-random factors, and dubs this a natural experiment. Group 5 does some bench science and comes up with a plausible pathway by which X causes cancer. If three or four of these things all point in the same direction, we begin to think it would be smart to avoid X. <br /><br />I completely agree with you that we need theory, and that some of the things we test are more about socio-politics than science. It's clear, to me at least, that residential segregation has far more to do with cardiovascular disease than coffee does (or doesn't). But good luck untangling that web of causality. Or, on second thought, wish me luck; it's my dissertation. <br />Geoff Doughertynoreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-80814257075117098222015-05-14T18:28:52.589-04:002015-05-14T18:28:52.589-04:00Geoff,
It isn't always exactly as you very cle...Geoff,<br />It isn't always exactly as you very clearly outline are issues in many life and health sciences. I recently learned of, and have read, a book by Milton Rothman called Discovering the Natural Laws. It's not a new book, but it shows how the 'laws' of physics were tested and developed. There, a basic principle is 'triangulated' by various experimental designs and so on, and the underlying principle is homed in on with asymptotically increased precision. With a good theory to test, an a prior theory one might say, we can refine our understanding and see if the theory really is correct, etc.<br /><br />There are issues and uncertainties in physics, certainly, but this basic process is not, in areas we're discussing, how things work. Here we don't have adequate theory to test. We compare internally (cases vs controls, drinkers vs non-drinkers). There seems little interest even in developing an adequate theoretical basis, and we borrow methods developed for truly replicable phenomena, as we often say here. Or, our theory that things are not replicable is not being understood, accepted, or used adequately. Therein lies many of our problems and issues, I think.<br /><br />When, how, or whether we can develop an adequate theory to test is an open question. Why we persist in what we're doing is a separate question that, in my view again, is about the sociopolitics of current science as much as it is about the science itself.Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-52083279229522171442015-05-14T18:12:09.251-04:002015-05-14T18:12:09.251-04:00Geoff, thanks so much for your detailed comments. ...Geoff, thanks so much for your detailed comments. Absolutely. Or, one population drinks Dunkin Donuts coffee Coolatas and the other drinks espresso, but they are both called 'coffee'; your definition of heart disease is different from mine; when you started to drink coffee is in fact the crucial factor, but people don't remember that accurately; older people used to drink instant coffee (say), and that was in fact the cause of the findings of coffee being a risk factor. And so on. <br /><br />I don't find it surprising that this is just the way things go. Our methods are good when risk factors are strong (cholera, HIV, Ebola), but not so good when everyone is unique and risk factors have weak effects. Science is better when all observations are replicable, and that just doesn't happen in epidemiology or genetics. Throw on top of that all the other issues that we've mentioned, and, well, should I have that after dinner cup of coffee or shouldn't I? Anne Buchananhttps://www.blogger.com/profile/09212151396672651221noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-2945063063412192092015-05-14T17:57:57.044-04:002015-05-14T17:57:57.044-04:00Before attributing the back-and-forth results on c...Before attributing the back-and-forth results on coffee to study design, it's probably worth unpacking study design a bit. <br /><br />First, while randomized trials are inevitably referred to as the "gold standard" of causation, they, too, can yield misleading results. The people who participate in RCTs are invariably not the same people for whom we'd like to make inferences about coffee and stroke. The RCT folks are healthier, wealthier and better educated, so a finding in one direction or another from an RCT may not represent the underlying population value. <br /><br />Secondly, even though an RCT might direct someone to drink X cups of coffee per day, the reality is that trial participants never do exactly what they're told, and so you're left to either analyze the data based on their actual behavior, which breaks the randomization process and opens the results to confounding, or to analyze based on the exposure they were assigned to, which inevitably makes it more likely that you will miss any real effect that might be present in the data. <br /><br />While some of the studies mentioned by Carroll might have been case-control studies, many were either cross-sectional or cohort studies, which means people were asked about coffee consumption contemporaneously, before they got sick. <br /><br />This limits the possibility for recall bias.<br /><br />That said, measuring exposures is tough to do, particularly when they involve what we eat or drink. But unless the error is somehow associated with the outcome (People on the verge of heart disease systematically report more coffee consumption), this type of thing will mostly bias the study results toward the null. <br /><br />Confounding is always an issue. I haven't read all of these studies, but I strongly suspect they all controlled for smoking, BMI, statin use, age, gender, and other well-known predictors of disease that could also be associated with coffee. So the main potential for bias arises with unknown/unmeasured confounders<br /><br />The nice thing about unknown confounders is that they're mostly caused by the same thing as known confounders (i.e., bad health), so adjusting for known confounders often yields an accurate result. <br /><br />So, if we can't blame confounding or measurement error, what can we blame? The list is long: <br /><br />* Small study size. Smaller studies are more likely to generate extreme results, so it's no surprise to see a series of studies w/ low N ping-ponging back and forth across the risk/no risk line<br /><br />* Different populations. If I study coffee in white women under 40 and you study it in black men over 40, we may get different results. The resulting headline will likely read "Coffee is dangerous/healthy" regardless of the specifics of the population<br /><br />* Different exposures. I decide to study what happens to people who drink more than four cups of coffee a day. You decide to study the effect of any coffee consumption vs. none. Unsurprisingly, we get different results<br /><br />* Different outcomes. I happen to have data on ischemic stroke lying around, and I decide to do a study on association with coffee. You have data on people with hemorrhagic stroke. Our analyses point in different directions, and again result in duellng headlines: "Coffee prevents/causes stroke!"<br /><br />The big surprise here, to me anyway, is how consistent this is with the way things go in almost all scientific endeavors. Someone does a study. Someone else thinks that if they address the same question in a different way, or with different data, they might get a better/different answer. They do it, and their colleagues try to reconcile the competing results. They come up with an explanation and test it, and thus the cycle continues.Geoff Doughertynoreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-89061940838922509632015-05-14T13:04:24.770-04:002015-05-14T13:04:24.770-04:00Yes, and a few years ago it was wine, then eggs, t...Yes, and a few years ago it was wine, then eggs, then butter, then cholesterol, then salt. As Hippocrates said some 3000 years or so ago, moderation in all things! And don't read the 'science' news; it will just upset you---and that really IS bad for your health!Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-78072122386408234182015-05-14T12:59:57.713-04:002015-05-14T12:59:57.713-04:00There were times when I would drink couple of cups...There were times when I would drink couple of cups per day, other times I would avoid coffee. However what stuck with me is that coffee is bad for you. So it's kind of like when I drink coffee, I feel guilty. This is not a good thing, considering how many studies indicate that it's healthy to drink coffee in moderation. However I guess the health industry did its job properly and I just feel that coffee is unhealthy. Recently I read a blog post stating that 15-20 minutes of a powernap is much more energizing than a cup of coffee. I have mentioned this and got a great response - coffee is like a quirky habit, routine that you love doing. So why give up I ask =)Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-84134934589476840422015-05-14T12:00:04.678-04:002015-05-14T12:00:04.678-04:00Yes, and no decaf fake stuff for me, either! But w...Yes, and no decaf fake stuff for me, either! But we mostly drink tea (until someone shows that that's really, really bad for you!).Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-64877612660701138042015-05-14T11:46:24.984-04:002015-05-14T11:46:24.984-04:00Sounds like you're both on coffee, for the goo...Sounds like you're both on coffee, for the good or bad of it.Holly Dunsworthhttps://www.blogger.com/profile/05260104967932801186noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-32239243921377462902015-05-14T09:54:18.856-04:002015-05-14T09:54:18.856-04:00YES! I'll drink a cup, and then have a heart ...YES! I'll drink a cup, and then have a heart attack or not, then drink another cup, ... and so on. If I eventually have a coronary, then we know coffee's the cause. If not, then we know coffee protects!<br /><br />Simple as, well, simple as a typical story in Science or Nature!Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-88101670173824569452015-05-14T09:50:55.899-04:002015-05-14T09:50:55.899-04:00I have an idea. Do you think Nature would publish...I have an idea. Do you think Nature would publish it? We could do n of 1 studies on coffee drinking. Anne Buchananhttps://www.blogger.com/profile/09212151396672651221noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-17964233743641715582015-05-14T09:44:05.290-04:002015-05-14T09:44:05.290-04:00We are, collectively, in my opinion not asking wha...We are, collectively, in my opinion not asking what physicists call well-posed questions. We are assuming physics and chemistry-like replicability, orderly probability distributions reflecting causal factors, and so on. These are unrealistic, and maybe that fact is itself the deeper truth. Maybe there just is no simple causal-effect predictability of the sort people are naturally wishing for.Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-30961671399466071312015-05-14T09:38:26.388-04:002015-05-14T09:38:26.388-04:00I just realized that the causation problem is a .....I just realized that the causation problem is a ... problem... for studying how/whether scientific findings affect our dietary habits. Meh. I'm going back to grading now. Holly Dunsworthhttps://www.blogger.com/profile/05260104967932801186noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-34327717290723899842015-05-14T09:24:19.871-04:002015-05-14T09:24:19.871-04:00It's all the same story, when it comes to comp...It's all the same story, when it comes to complex causation, which even this is about. It has more to do with maintaining the research establishment and its supporting industries than with actual results or public health science. If we were doing what was really needed, it would include actually figuring out real cures for clearly genetic disease, for example, or real ways to change behavior that leads to serious common disease. Coffee is not the problem, nor the cure (except for putting us in a better mood).Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-29737993423805535412015-05-14T09:09:58.288-04:002015-05-14T09:09:58.288-04:00Not to continue spouting off, but, yes, to continu...Not to continue spouting off, but, yes, to continue...<br /><br />What this begs for, at least to me, is proof (by whom, from whom?) that these scientific studies, which I believe are eligible for larger pots of public funding are actually more worthy of it than ones that are seen as "just" for the sake of knowledge, like paleontology. Because at this point, this stuff is "just" for the sake of knowledge too. Isn't it?Holly Dunsworthhttps://www.blogger.com/profile/05260104967932801186noreply@blogger.com