VALIDATION OF ZYGOSITY ASSESSMENT BY A SELF-REPORT QUESTIONNAIRE IN A SAMPLE OF ADULT SERBIAN TWINS

Validation of a twin zygosity-estimating questionnaire, The Questionnaire of Twins’ Physical Resemblance, created by Oniszczenko et al. and used in European and Serbian twin studies, was carried out on a sample of 222 pairs (176 monozygotic, 46 dizygotic) of adult twins (average age 24.6). Four discriminant functions, use of different sets of indicators (zygosity questionnaire items), were applied in order to obtain the most correct and accurate estimates of zygosity. The first function was a predefined function used in European twin studies, the following two functions contained sets of 18 and 24 freely estimated indicators respectively, while the last one utilized the items with most consistent contributions to zygosity prediction. The analytic procedure included cross-validation, whereby the sample was randomly split into two subsamples, comprising 107 and 115 twin pairs. The results pointed to successful (over 90% correct) identification of monozygotic twins, and sizeably lower correctness in identifying dizygotic twins. Overall correctness of estimation exceeded 90%, with the small set of best-performing indicators. The results encourage questionnaire estimation of zygosity, and raise the issue of improving the classification procedure in dizygotic twins.

Setting up and utilizing Norwegian twin panels

In the late 1970s, a Norwegian twin panel was set up. It included all like-sexed twin pairs, born in the period<br />1915 to 1960, where both members were alive and had a known address in Norway at the time. The work<br />was initiated through a grant from the National Institutes of Health in the United States. The aim was to estimate<br />maternal effects to understand the causes of variation in traits and diseases that originate in pregnancy.<br />However, the twin panel was also utilized for estimating genetic and environmental effects on a series of<br />phenotypes, for instance lipoproteins, receptors, coagulation factors, cognitive abilities, educational attainment<br />and left-handedness. A short zygosity questionnaire was sent together with the first invitation letter to<br />the twins. Later questionnaires on general health, lifestyles and pregnancy outcomes were sent out. One<br />important finding was that the fetal genotype had much stronger influence on variation in fetal growth than<br />what had been assumed previously. In the early 1990s, the New Norwegian Twin Panel was created, based<br />on information on plural births in the Medical Birth Registry of Norway (MBRN). The panel included both<br />like-sexed and opposite-sexed pairs born in the years 1967 to 1974. After linking the MBRN to present<br />addresses, using a national identification number, a questionnaire on zygosity, with a few items on health<br />and social background, was sent out. This panel was later expanded to include twins born 1975-1979 and to<br />collect more data on health, well-being and lifestyle factors. The data have been utilized for a series of subprojects,<br />including psychiatric interviews and the collection of DNA samples. Linkage to Norwegian health<br />registries has provided important research opportunities for a variety of phenotypic outcomes.

Determining Zygosity in the Vietnam Era Twin Registry: An Update

Our work assessed the accuracy of the original zygosity classification in the Vietnam Era Twin (VET) Registry using new information from DNA markers on a subset of participants. We then constructed an updated zygosity classification algorithm. The VET Registry includes 7,375 male–male twin pairs who served in the military during the Vietnam era. During the mid-1980s 4,774 twin pairs completed a zygosity questionnaire of 20 items. Additionally, military record information, including blood group, was available. Items from the zygosity questionnaire and blood group were used in the original zygosity classification. Between 1990–2009 DNA was obtained from 612 twin pairs and concordance between co-twins was used to classify zygosity. Next logistic regression was used to construct predicted probabilities of zygosity using items from the zygosity questionnaire with this subsample. All twins were reclassified according to the new zygosity prediction model and compared with the original zygosity assignment. The original and new predicted probabilities of zygosity were highly correlated (r= 0.962) and concordance for the classification of zygosity was similarly high (kappa = 0.936). Errors in the original zygosity assignment were primarily due to monozygotic twins that were misclassified as dizygotic based on military record blood group data. Removing the military record blood group data markedly improved the accuracy of the original classification. Zygosity assignment based on a zygosity questionnaire was highly predictive of DNA-based zygosity. Augmentation of such a zygosity classification from administrative data, military records, or other records, should be done with caution.

Validity of the Zygosity Questionnaire and Characteristics of Zygosity-Misdiagnosed Twin Pairs in the Healthy Twin Study of Korea

Determining valid zygosity is a basic and important requirement in a twin study, because misdiagnosing zygosity leads to biased results. The Healthy Twin Study has collected data from adult like-sex twins and their families since 2005. In the study, a questionnaire to determine zygosity was developed comprising four questions; one concerning the degree of resemblance, and three concerning the degree of confusion by the resemblance. Among 2,761 individuals (624 twin pairs) of twin and their families, 406 pairs of twins (mean age 38.3, 63.5% women) with both questionnaire and genotype information were selected to examine the validity of the zygosity questionnaire using 16 short tandem repeat markers. We first determined individual zygosity including undetermined category, and then decided the zygosity of a twin pair using a decision tree. Sensitivity of questionnaire diagnosis was 98.8% for monozygotic (MZ) and 88.9% for dizygotic (DZ) twins, and positive predictive value was 97.2% for MZ and 95.0% for DZ. When we compared correctly and wrongly diagnosed twin pairs, misdiagnosed DZ twins (nine pairs) showed striking similarity in stature or obesity even exceeding that of true MZ twins. Our finding suggests that a parsimonious questionnaire method of diagnosing the zygosity will be useful, and adding physical or physiological measurements to a questionnaire of zygosity diagnosis will either confound the correct diagnosis or reduce the efficiency of the study compared with using questionnaire alone or with introducing genotyping.

Healthy Twin: A Twin-Family Study of Korea — Protocols and Current Status

Abstract‘Healthy Twin’ is a twin family study extension of the existing Korean Twin-Family Register. Healthy Twin recruits adult like-sex twins over the age of 30 and their adult family members. Healthy Twin protocols are primarily tailored to the study of the quantitative trait loci of complex traits as well as to the role of environment in the etiology of complex diseases. A full-length survey is underway, including questionnaires, health examinations and the collection of biological specimens. So far, 820 individuals (169 twin pairs and their families) have participated in the survey and 1068 individual twins (608 twin pairs) have replied to the mailed zygosity questionnaire as of July 2006. The first phase (2005–2006) of Healthy Twin will recruit 1550 individuals (including about 380 twin pairs), and the second phase a proposed 1500 to 2500 additional participants. We report study protocols and zygosity and the distribution of family size of the study participants.

Determination of Twin Zygosity: A Comparison of DNA with Various Questionnaire Indices

This study examined cross-validation and test-retest reliability of questions and questionnaire indices commonly used for twin zygosity classification. Mothers of 58 monozygotic (MZ) and 52 dizygotic (DZ) same sex twin pairs were interviewed by telephone to answer questions regarding the similarity of their twins (mean age = 14.6 ± 2.8 years). A logistic regression equation correctly classified 91% of both MZ and DZ twin pairs in our sample using 7 of the 12 zygosity questions. The internal consistency for the total questionnaire (Cronbach's alpha) was 0.88. The median two month temporal stability estimate for the individual questions was r = .56 and r = .79 for the test total. For the cross-validation, zygosity classification indices taken from 9 previous studies were applied to our sample and compared to classification according to DNA microsatellite analyses (agreement range = 44 to 100%). The accuracy of the classification indices was significantly lower than the original studies for 62% of the comparisons. If zygosity determination with DNA markers or blood group typing for all subjects is not feasible, rather than using classification indices based on other studies, an optimal classification scheme can be achieved by using a zygosity questionnaire of which the reliability and validity of the questions is established in a random subsample of the same twin cohort.