<<Disclaimer: Verify this information before applying it to your situation.>> Part 1- Twin Studies The occurrence of CD in twins will be important to the understanding of any role commensal microflora play in the onset of CD. Ideally, it is easiest to study the effects of specific commensal bacteria on the gut and gut development through the use of specially bred germ-free (gnotobiotic) laboratory animals. This allows researchers to study the effects of only one or a few microbes at a time. There are typically some 500 varieties of bacteria colonizing the human gut which makes studying the effects of specific microflora difficult. Since no gnotobiotic humans are available, comparisons of the microflora in identical (monozygotic) twins, where one has CD and the other does not, provides one approach to identifying microbes which may play a role in the onset of CD. To this end, an understanding of twin studies is in order. I received the following reply to one of my posts: ---------- Re: Antibiotics a Possible Trigger of Crohn's Disease Dear Roy, Wife and I have been reading many of your posts. In this item you mention that identical twins don't have CD. I think that if you check further, that research has shown that although both may not have CD at any one time, that the twin without the CD does eventually come down with CD. Hal ---------- While twin studies show there is a high concordance of CD in identical twins, there are no studies showing that CD eventually occurs in both identical twins if only one has it at one time. And this is true in one study of 5 twin pairs followed up for 11-23 years where 2 of the twins remained free of CD. The fact that CD may occur in identical twins at different times in their lives further supports that environmental factors, such as commensal microflora, are necessary to trigger the onset of CD. When looking at the data in twin studies, it is important to be able to understand the data. Twin pairs are selected for such studies where at least one manifests the disease under study. An affected person ascertained independently of his relatives in a genetic study is called a "proband". The twin presenting the disease resulting in the selection of a twin pair for the study is the "proband". The concordance rate, the percentage of twins found to both have the same disease, is the result generally sought. Twin studies generally look at both monozygotic (identical) and dizygotic (maternal) twins. High concordance in monozgotic twins and low concordance in dizygotic twins suggests a significant genetic involvement. When concordance rates are low and nearly equal, environmental factors may be more important. Concordance rates are expressed in two ways: pairwise and probandwise. The pairwise rate is the percent or proportion of twin pairs in a study who are found to both have the disease. The probandwise rate is the percent chance that if one twin has the disease the other twin also has the disease. Statistics can be a little confusing so let's go through an example. The largest CD twin study to date has only involved 47 twin pairs. (Of these, the abstract doesn't say how many were monozygotic and dizygotic.) The study found the concordance rates were, monozygotic, (0.86 probandwise and 0.75 pairwise) and, dizygotic, (0.20 probandwise and 0.11 pairwise). This means the following: Using the 0.75 pairwise concordance rate above, if we have 100 pairs of monozygotic twins where at least one twin has CD, we expect 75 of those pairs will be concordant, and 25 pairs discordant. There are a total of 200 individual twins in this example. Out of those individuals, 150 concordant twins have CD and 25 discordant twins have CD. 175, (150+25), total individual twins have CD. Let's just take those 175 individual twins with CD and place them in a room. We know that 150 of those individuals are concordant, both having CD. So out of those 175 individual twins, 150 have a sibling twin who also has CD. If one twin is randomly selected out of those 175 twins, there is a 150 out of 175 chance that the selected twin has a sibling twin with CD. 150/175 = 0.86, so there is an 86% chance that if one twin with CD is selected, his or her sibling twin will also have CD. This is the probandwise rate given above, and that is the chance that if one identical twin has CD, the other twin also has it. Twin CD studies have been pretty small. Even this largest study has only 47 pairs. How much confidence can be placed in such small sample studies? In this study it was concluded the risk of being concordant for celiac disease estimated for the non-index twin of monozygotic pairs was 17 (95% confidence interval 2.1-134). If I understand this correctly, that means that the risk of having CD for one identical twin if the other twin has CD is 17 times more than the risk rate for CD in the general population (1/133 in the USA) or 17/133. What is disturbing is that the 95% confidence interval ranges from 2.1/133 to 134/133, or a risk rate anywhere between 2% to 100% or so. That doesn't seem very confident to me. Following are some articles on CD twin studies plus a couple of Crohn's disease twin studies for comparison: ---------- DISSECTING GENETIC SUSCEPTIBILITY TO GLUTEN SENSITIVITY: HLA-LINKED RISK FACTORS IN COELIAC DISEASE AND DERMATITIS HERPETIFORMIS KATI KARELL ACADEMIC DISSERTATION FINNISH RED CROSS BLOOD TRANSFUSION SERVICE AND FACULTY OF SCIENCE, DEPARTMENT OF BIOSCIENCES, DIVISION OF GENETICS, UNIVERSITY OF HELSINKI, FINLAND To be publicly discussed, with permission of the Faculty of Science of the University of Helsinki, in the Nevanlinna Auditorium of the Finnish Red Cross Blood Transfusion Service, Kivihaantie 7, 00310 Helsinki, on April 25th 2003, at 12 o'clock. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/karell/dissecti.pdf ---------- Gut. 2002 May;50(5):624-8 The first large population based twin study of coeliac disease. Greco L, Romino R, Coto I, Di Cosmo N, Percopo S, Maglio M, Paparo F, Gasperi V, Limongelli MG, Cotichini R, D'Agate C, Tinto N, Sacchetti L, Tosi R, Stazi MA. Department of Paediatrics, University of Naples Federico II, Naples, Italy. [log in to unmask] BACKGROUND AND AIMS: The genetic load in coeliac disease has hitherto been inferred from case series or anecdotally referred twin pairs. We have evaluated the genetic component in coeliac disease by estimating the concordance rate for the disease among twin pairs in a large population based study. METHODS: The Italian Twin Registry was matched with the membership lists of a patient support group. Forty seven twin pairs were recruited and screened for antiendomysial (EMA) and antihuman-tissue transglutaminase (anti-tTG) antibodies; zygosity was verified by DNA fingerprinting and twins were typed for HLA class II DRB1 and DQB1 molecules. RESULTS: Concordance rates for coeliac disease differ significantly between monozygotic (MZ) (0.86 probandwise and 0.75 pairwise) and dizygotic (DZ) (0.20 probandwise and 0.11 pairwise) twins. This is the highest concordance so far reported for a multifactorial disease. A logistic regression model, adjusted for age, sex, number of shared HLA haplotypes, and zygosity, showed that genotypes DQA1*0501/DQB1*0201 and DQA1*0301/DQB1*0302 (encoding for heterodimers DQ2 and DQ8, respectively) conferred to the non-index twin a risk of contracting the disease of 3.3 and 1.4, respectively. The risk of being concordant for coeliac disease estimated for the non-index twin of MZ pairs was 17 (95% confidence interval 2.1-134), independent of the DQ at risk genotype. CONCLUSION: This study provides substantial evidence for a very strong genetic component in coeliac disease, which is only partially due to the HLA region. Publication Types: Twin Study PMID: 11950806 [PubMed - indexed for MEDLINE] ---------- Continued in Part 2 *Support summarization of posts, reply to the SENDER not the Celiac List*