Announcement

Collapse
No announcement yet.

Polygenic Inheritance of AIS

Collapse
X
 
  • Filter
  • Time
  • Show
Clear All
new posts

  • #16
    Separating the scientists from the folkscientists

    http://genomemedicine.com/content/2/2/10/

    Conclusions

    In this paper we set out to compare different models that combine the effects of multiple risk loci into an overall genetic risk. We conclude that a model that is additive or multiplicative on the risk scale across all loci is incompatible with the observed recurrence risks to relatives. The constrained multiplicative (CRisch), Odds and Probit models are all compatible with the observed data and, in fact, it is difficult to distinguish between them when the relative risk at an individual locus is small. Importantly, we show that the unconstrained multiplicative (Risch) model, often used in theoretical studies because of its mathematical tractability, is not a realistic model as impossible probabilities of disease are implied. Specifically, the multiplicative Risch model generates a relationship of = 1, but we have demonstrated that this not possible under many disease scenarios and occurs in the theoretical derivation because probabilities of disease are not constrained and can exceed 1. We have demonstrated that under more realistic models in which probabilities of disease are constrained to 1, the ratio is often much less than 1, a result that is consistent with empirical estimates from a range of diseases. Finally, we conclude that it will only be possible to distinguish between the CRisch, Odds and Probit models in practice if genetic risk profiles are able to reconstruct the majority of the known genetic variance; this is unlikely for the foreseeable future.
    (emphasis added)

    Please note the above article has a real chance of being false.
    Sharon, mother of identical twin girls with scoliosis

    No island of sanity.

    Question: What do you call alternative medicine that works?
    Answer: Medicine


    "We are all African."

    Comment


    • #17
      Downs Syndrome

      Rohrer1

      Like you said, Downs Syndrome isn't caused by heredity. It's caused because healthy genes are "scrambled" during assembly. Scientists don't know why this happens. Downs is far different from Cystic Fibrosis or Sickle Cell which are caused by heredity. Ogilvie is suggesting that Scoliosis is caused by heredity. Unfortunately for his hypothesis no childhood genetic disease hits 2%+/- of children around the world. Ogilvie is going to be wrong, and when he's proven wrong remember that you heard it here first.

      There is an outside chance that some rare types of Scoliosis are caused by heredity. However this type won't hit more than one children in several thousand. Realistically it won't hit more than one child in tens or even hundreds of thousands. Only a handful of potentially fatal genetic diseases hit more than one child in ten thousand and to the best of my knowledge they are all regional.

      Don't be disappointed to find out it is hereditary, so many good things are, too.
      Now you are on the right track. Beneficial traits are spread through heredity, negative traits (at least in children) are caused by environment. That's what Darwin found on the Galapagos islands 150 years ago. If you bet that way you'll be right 99.9% of the time.
      Last edited by Dingo; 05-02-2010, 12:01 PM.

      Comment


      • #18
        Originally posted by Dingo View Post
        ... no childhood genetic disease hits 2%+/- of children around the world.
        False.

        .
        .
        Sharon, mother of identical twin girls with scoliosis

        No island of sanity.

        Question: What do you call alternative medicine that works?
        Answer: Medicine


        "We are all African."

        Comment


        • #19
          AIS book

          Rohrer01

          If you can get your hands on a genetics textbook and really study it through, it will help you a LOT to understand what is going on with your son.
          Could you send me a link to the book or article that explains the genetic cause of Adolescent Idiopathic Scoliois? It would help me a ton. I'll forward it to Dr. Ogilvie. It will advance his research by at least 20 years and allow him to avoid a lot of pesky experiments and papers.

          Look, idiopathic means of unknown cause. Nobody knows what causes Scoliosis and that includes Dr. Ogilvie.

          Dr. Alain Moreau has published work that shows that Melatonin Signaling Dysfunction may be the cause of AIS. For some reason this nervous system disorder causes a buildup of Osteopontin which leads to Scoliosis. As far as I know he doesn't know the cause of this disorder.

          If his work is correct the next question is are identical twins 100% concordant for Melatonin Signaling Dysfunction? That will tell us a lot.
          Last edited by Dingo; 05-02-2010, 12:29 PM.

          Comment


          • #20
            Danish twin study

            Rohrer01

            You might find this twin study from Denmark interesting.

            Spine (Phila Pa 1976). 2007 Apr 15;32(8):927-30.
            Adolescent idiopathic scoliosis in twins: a population-based survey.
            STUDY DESIGN: A questionnaire-based identification of adolescent idiopathic scoliosis (AIS) patients in a twin cohort. OBJECTIVE: The purpose of this study was to establish a scoliosis twin cohort to provide data on the heritability of AIS. SUMMARY OF BACKGROUND DATA: The etiology of AIS is still unclear, and the true mode of inheritance has yet to be established. Concordance rates in monozygotic twins have been reported to be between 0.73 and 0.92, and in dizygotic twins between 0.36 and 0.63. Studies on concordance in twin pairs provide a basis for analyzing the influence of genetic versus environmental factors. METHODS: All 46,418 twins registered in the Danish Twin Registry born from 1931 to 1982 were sent a questionnaire, which included questions about scoliosis. A total of 34,944 (75.3%) representing 23,204 pairs returned the questionnaire. RESULTS: A subgroup of 220 subjects considered to have AIS was identified, thus giving a prevalence of 1.05%. The concordant twin pairs were all monozygotic. Pairwise, the concordance rate was 0.13 (13%) for monozygotic and zero for dizygotic twin pairs; proband-wise concordance was 0.25 for monozygotic and zero for dizygotic pairs. The concordance of monozygotic and dizygotic pairs was significantly different (P < 0.05). CONCLUSION: We have found evidence for a genetic etiology in AIS, but the risk of developing scoliosis in 1 twin whose other twin has scoliosis is smaller than believed up until now.
            Just 13%? That's not even half as high as Multiple Sclerosis which they know is triggered by the environment. Even if these researchers missed 300% of the cases (which I doubt) MZ concordance would still be just 50% or so. That's low. To the best of my knowledge no other large twin study on Scoliosis has ever been performed. If any exists please post it here because I'd love to read it.
            Last edited by Dingo; 05-02-2010, 04:19 PM.

            Comment


            • #21
              Originally posted by Dingo View Post
              Rohrer01

              You might find this twin study from Denmark interesting.

              Spine (Phila Pa 1976). 2007 Apr 15;32(8):927-30.
              Adolescent idiopathic scoliosis in twins: a population-based survey.


              Just 13%? That's not even half as high as Multiple Sclerosis which they know is triggered by the environment. Even if these researchers missed 300% of the cases (which I doubt) MZ concordance would still be just 50% or so. That's low. To the best of my knowledge no other large twin study on Scoliosis has ever been performed. If any exists please post it here because I'd love to read it.
              This paper is dismissed IN PRINT by researchers in this field for reasons that are obvious to people not even in the field.

              This paper needs to be retracted by the journal. It is annoying to other researchers to have to continually mention it just to shoot it down. This paper is aberrant in the field of these types of papers and yet Dingo singles out the one aberrant paper simply because it matches his preconceived notions. This is a textbook folkscience approach to science.

              Dingo constantly posts it because he fails to understand why researchers dismiss this study. It's just more folkscience on his part in lieu of real science because he has no relevant training. And it shows.

              A more accurate figure for occurrence in monozygotic twins comes from a meta analysis and is ~73%. This same paper shows about a 1/3 chance of non-monozygotic siblings having scoliosis. This is in keeping with a genetic trigger.
              Sharon, mother of identical twin girls with scoliosis

              No island of sanity.

              Question: What do you call alternative medicine that works?
              Answer: Medicine


              "We are all African."

              Comment


              • #22
                Another interesting paper

                2008: Understanding Genetic Factors in Idiopathic Scoliosis, a Complex Disease of Childhood

                Is IS Genetic?

                The recognition of genetic influences in IS is well-documented [19-25]. Familial forms of IS were described as early as 1922 [26]. Since then, reports of multiple twin sets and twin series have consistently shown higher concordance in monozygotic (MZ) compared to dizygotic (DZ) twins (reviewed in [27]). A meta-analysis of these clinical twin studies revealed 73% MZ compared to 36% DZ concordances [28]. Interestingly, in this series there was a significant correlation with curve severity in monozygous twins (P<.0002), but not dizygous twins. No correlation with curve pattern was found, suggesting the importance of genetic factors in controlling susceptibility and disease course, but not necessarily disease pattern. More recently, Andersen et al. [29] reported their findings using the Danish Twin Registry. They found 25% proband-wise concordance in monozygotic twins (6 of 44 concordant) compared to 0% concordance (0 of 91) in dizygotic twins, with an overall prevalence of approximately 1%. The lower concordances in both groups as compared with prior results may be explained by differences in study design, specifically, ascertainment in clinics versus by registry, and screening by examination versus questionnaire. Nevertheless the overall trend obtained for all studies suggests strong genetic effects in IS. Interestingly, measured concordances in monozygotic twins were below 100%, reflecting the complexity of disease and suggesting the involvement of as yet unknown environmental or stochastic factors in disease susceptibility.
                Anybody who reads this stuff can see which way the train is headed. Genetic susceptability plus environmental damage is the template for nearly all chronic disease in children and young adults.

                I look forward to the next, large twin study.

                Comment


                • #23
                  Originally posted by Dingo View Post
                  Could you send me a link to the book or article that explains the genetic cause of Adolescent Idiopathic Scoliois? It would help me a ton. I'll forward it to Dr. Ogilvie. It will advance his research by at least 20 years and allow him to avoid a lot of pesky experiments and papers.
                  Here we have an untrained lay person thinking he can "help" a researcher advance his research 20 years and allow him to avoid a lot of pesky experiments and papers.

                  This arguably gives the other pseudoscientists a run for their money for pure unadulterated arrogance combined with pure unadulterated ignorance.

                  Spectacular.
                  Last edited by Pooka1; 05-03-2010, 01:55 PM.
                  Sharon, mother of identical twin girls with scoliosis

                  No island of sanity.

                  Question: What do you call alternative medicine that works?
                  Answer: Medicine


                  "We are all African."

                  Comment


                  • #24
                    Originally posted by Dingo View Post
                    Rohrer1

                    Like you said, Downs Syndrome isn't caused by heredity. It's caused because healthy genes are "scrambled" during assembly. Scientists don't know why this happens. Downs is far different from Cystic Fibrosis or Sickle Cell which are caused by heredity. Ogilvie is suggesting that Scoliosis is caused by heredity. Unfortunately for his hypothesis no childhood genetic disease hits 2%+/- of children around the world. Ogilvie is going to be wrong, and when he's proven wrong remember that you heard it here first.

                    There is an outside chance that some rare types of Scoliosis are caused by heredity. However this type won't hit more than one children in several thousand. Realistically it won't hit more than one child in tens or even hundreds of thousands. Only a handful of potentially fatal genetic diseases hit more than one child in ten thousand and to the best of my knowledge they are all regional.


                    Now you are on the right track. Beneficial traits are spread through heredity, negative traits (at least in children) are caused by environment. That's what Darwin found on the Galapagos islands 150 years ago. If you bet that way you'll be right 99.9% of the time.
                    Dingo, WHAT are you "reading" in to what I said to so grossly misquote me. I NEVER said that Down's Syndrom is not hereditary. It is quite obvious that it IS. Here is what I said....again.

                    "Dingo, I am only partially quoting you to make a point. What you say here may be true for some diseases, but it is a proven FACT that it doesn't hold true with all genetic disorders. Down's Syndrome is a genetic disease causeed by a trisomy (meaning there are three copies of a chromosome). However, genetics is more complicated than that. During cell division, sometimes there is not a complete trisomy and only a partial where a piece of one chromosome attaches itself to another chromosome. If it is the right peice, you can still have a child with Down's Syndrome. There is nothing that can trigger someone with this genetic makeup to suddenly express the symptoms of Down's Syndrome. Either the child has it or he/she doesn't. What the environment can do is if the child is worked with intensely, then the child's full intellectual potential can be brought out. This does not negate the fact that the child has Down's Syndrome with all of it's risks including heart problems. If a person with Down's Syndrom has a child with a non-down's person. The baby has a 50/50 chance of having Down's. Genetic disorders are not always triggered by something in the environment. Some are, but a vast amount are not. I think that you are trying to prove in your mind somehow that scoliosis could have been avoided if...."

                    Bold added by ME.

                    And WHO ever said that only good traits are passed on through heredity and bad traits are caused only by environment...but you???? I'm trying to by nice, but where are you getting this stuff? I give you credit for attempting to read scientific papers, but you are clearly not understanding them. You have a preconceived notion in your head that no amount of proof can seem to dispell.

                    There are also several genetic reasons why we don't get 100% concordance in monozygotic twins. At this point, I am not even going to try to explain these to you. Sorry.

                    As far as getting a textbook on AIS genetics, I have no idea where to find one. You might try the book store. But IF you find one, chances are it will have been written by Dr. Ogillvie.

                    I suggested that you go to a University Campus Bookstore and see about getting a genetics textbook for free. Sometimes they give them away when they switch to a newer edition. You just have to catch them just right. As I stated, I have picked up many books, on various subjects, that way. The content usually isn't that much changed and the basic information will certainly be the same.

                    Sorry if this was harsh. I don't like being misquoted, as others don't like it either.

                    I will give you one more example of how science works. I worked for three years on a undergrad project. My professor was convinced that another professor was wrong in his findings about certain "gene" interactions. During the course of the research, we actually proved the other professor was right...WHAT??? He was right? Does that mean we stopped there. Yes, as far as trying to prove his theory to be incorrect. We didn't stop running tests in a different direction, though. We found information that the other professor had not discovered about a different ineraction between these two "genes". That's how science works. When something repeatedly comes up to prove something, then you have to just accept the facts and move on and try to understand more about, "What else is there to learn about this?"

                    I'm sorry but your hypothesis about good being genetic and bad being environmental is just wrong. You have no proof and you never will. There are too many genetic diseases out there. You need to understand what "genetic" means.

                    I'm not posting on this topic anymore.

                    Linda, thank you for the good and helpful information that you found for us.
                    Last edited by rohrer01; 05-03-2010, 09:49 AM.
                    Be happy!
                    We don't know what tomorrow brings,
                    but we are alive today!

                    Comment


                    • #25
                      agree to disagree

                      Rohrer01

                      I'm afraid we'll have to agree to disagree. If you ever run across a paper that explains how heredity causes AIS or any other widespread, deadly, childhood disease please post it here. I'd love to read it.

                      To start your search you might want to look through Wikipedia for a common, potentially life threatening childhood disease, caused by heredity. Wikpedia: List Of Genetic Disorders. Scoliosis hits about 2% of the population, try to find something comparable. Let me save you some time, nothing like that exists.

                      I should add that scientists routinely find genes that are associated with illness but most of the time they don't understand the mechanism that explains how the two are connected. Keep the following paper in mind the next time scientists discover a gene that "causes" a particular illness.

                      2008: Schizophrenia Susceptibility Genes Directly Implicated in the Life Cycles of Pathogens: Cytomegalovirus, Influenza, Herpes simplex, Rubella, and Toxoplasma gondii

                      Anyway I'm always interested in study or science links. Please post them as you come across them.
                      Last edited by Dingo; 05-03-2010, 10:40 AM.

                      Comment


                      • #26
                        Scientists and folkscientists always APPEAR to end up agreeing to disagree to due to the fact that only the scientists having relevant knowledge.

                        But the real reason is, just like why Dawkins refuses to debate creationists, it's just a waste of the scientist's time because there is no debate with two rational, knowledgable sides. There is one scientific side and one (or many) folkscience side(s). Apples and oranges.
                        Sharon, mother of identical twin girls with scoliosis

                        No island of sanity.

                        Question: What do you call alternative medicine that works?
                        Answer: Medicine


                        "We are all African."

                        Comment


                        • #27
                          Ignorance on the wing

                          Originally posted by Dingo View Post
                          Rohrer01
                          Scoliosis hits about 2% of the population, try to find something comparable. Let me save you some time, nothing like that exists.
                          False.

                          http://scoliosis.org/forum/showthread.php?t=10470
                          Sharon, mother of identical twin girls with scoliosis

                          No island of sanity.

                          Question: What do you call alternative medicine that works?
                          Answer: Medicine


                          "We are all African."

                          Comment


                          • #28
                            Originally posted by Dingo View Post
                            Rohrer01

                            To start your search you might want to look through Wikipedia for a common, potentially life threatening childhood disease, caused by heredity. Wikpedia: List Of Genetic Disorders. Scoliosis hits about 2% of the population, try to find something comparable. Let me save you some time, nothing like that exists.
                            I know I said I wouldn't post here again. But this statement draws me out once again. The reason you won't find a high percentage of children with potentially life threatening genetic disorders is simple. They DIE before they reach childbearing age. People with Down's are prevented by society from having children - although some still do, most do not. Scoliosis is not usually life threatening until it progresses to a very extreme degree, which generally is well beyond the childbearing years.

                            Also, NO ONE is saying that there is no chance that environment doesn't play a part in this at all. Mental illnesses are heritable diseases that can be triggered by emotional trauma. The trauma changes the brain chemistry which causes a cascade of reactions to turn on the "gene" for the illness. Things like that do happen. But we are talking about SCOLIOSIS, not mental illness.
                            Be happy!
                            We don't know what tomorrow brings,
                            but we are alive today!

                            Comment


                            • #29
                              stress and illness

                              rohrer01

                              Mental illnesses are heritable diseases that can be triggered by emotional trauma. The trauma changes the brain chemistry which causes a cascade of reactions to turn on the "gene" for the illness.
                              Stress probably impacts all disease, however I think you might be talking about this...

                              Child Abuse May 'Mark' Genes In Brains Of Suicide Victims

                              A team of McGill University scientists has discovered important differences between the brains of suicide victims and so-called normal brains. Although the genetic sequence was identical in the suicide and non-suicide brains, there were differences in their epigenetic marking – a chemical coating influenced by environmental factors.
                              "It’s possible the changes in epigenetic markers were caused by the exposure to childhood abuse"
                              Trauma, disease or a myriad of other environmental factors can harm our DNA just as it can harm our physical bodies. Nobody is immune from this type of damage or disease which is far different than heredity.

                              Comment


                              • #30
                                Originally posted by Dingo View Post
                                rohrer01



                                Trauma, disease or a myriad of other environmental factors can harm our DNA just as it can harm our physical bodies. Nobody is immune from this type of damage or disease which is far different than heredity.
                                If the trauma, disease, or other environmental factors cause damage to the DNA in the gametes(eggs or sperm), the disease then becomes and inherited one. This is so because the defective DNA can then be passed on to offspring. That's what heredity is. Therefore all heredity is not "good" as you have previously stated.
                                Be happy!
                                We don't know what tomorrow brings,
                                but we are alive today!

                                Comment

                                Working...
                                X