Verification of Self-Report of Zygosity Determined via DNA Testing in a Subset of the NAS-NRC Twin Registry 40 Years Later

The National Academy of Sciences – National Research Council (NAS-NRC) twin panel, created nearly 50 years ago, had twin zygosity determined primarily via a similarity questionnaire that has been estimated to correctly classify at least 95% of twins. In the course of a study on the genetics of healthy aging in the NAS-NRC twins DNA was collected for genome-wide scanning and zygosity confirmation was examined in 343 participating pairs. The sample was supplemented from two other studies using NAS-NRC twins where one or both co-twins were suspected to have Alzheimer disease or another dementia, or Parkinson’s disease. Overall there were 578 twin-pairs with DNA analyzed. 96.8% (519/536) had confirmation of zygosity assignment via questionnaire. Among 42 pairs whose questionnaire responses were inconclusive for assigning zygosity, 50% were found to be monozygous and 50% were dizygous. There was some evidence for greater misclassification of presumed DZ pairs in the healthy aging study where participation favored pairs who were similar in having a favorable health history and willingness to volunteer without any element of perceived risk for a specific disease influencing participation.