Please cite this article as follows: Virkud YV, Todd RD, Abbacchi AM, Zhang Y, Constantino JN. 2009. Familial Aggregation of Quantitative Autistic Traits in Multiplex Versus Simplex Autism. Am J Med Genet Part B 150B:328–334.
Familial aggregation of quantitative autistic traits in multiplex versus simplex autism†
Article first published online: 10 JUL 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 150B, Issue 3, pages 328–334, 5 April 2009
How to Cite
Virkud, Y. V., Todd, R. D., Abbacchi, A. M., Zhang, Y. and Constantino, J. N. (2009), Familial aggregation of quantitative autistic traits in multiplex versus simplex autism. Am. J. Med. Genet., 150B: 328–334. doi: 10.1002/ajmg.b.30810
- Issue published online: 17 MAR 2009
- Article first published online: 10 JUL 2008
- Manuscript Accepted: 12 MAY 2008
- Manuscript Received: 22 FEB 2008
- National Institute of Child Health and Human Development. Grant Number: HD42541
- Simons Foundation
- National Alliance for Autism Research (NAAR)/Autism Speaks. Grant Number: 1081
- National Institute of Mental Health. Grant Number: MH64547
- pervasive developmental disorders;
- social responsiveness scale;
- family studies;
- complex disease;
Recent research has suggested that the mode of inheritance for simplex autism (SA, one individual in the family affected) may be distinct from that for multiplex autism (MA, two or more individuals affected). Since sub clinical autistic traits have been observed in “unaffected” relatives of children with autism, we explored whether the distributions of such traits in families supported differential modes of genetic transmission for SA and MA autism. We measured patterns of familial aggregation of quantitative autistic traits (QAT) in children and parents in 80 SA families and 210 MA families, using the Social Responsiveness Scale. When considering all SA and MA siblings who scored below a uniform quantitative (clinical-level) severity threshold, MA brothers exhibited a distinct pathological shift in the distribution, compared to SA brothers (P < 0.0001). Such aggregation of QAT was also observed in fathers but not among females in MA families. Significant spousal correlations for QAT—suggestive of assortative mating—were observed in both SA and MA families, but neither group was characterized by a greater-than-chance level of concordant elevation among spousal pairs in this volunteer sample. Among male first degree relatives, there exist distinct patterns of QAT manifestation for simplex versus multiplex autism. These findings are consistent with the results of molecular genetic studies that have suggested differential modes of intergenerational transmission for SA and MA. Characterization of QAT and other endophenotypes among close relatives may be useful for reducing sample heterogeneity in future genetic and neurobiologic studies of autism. © 2008 Wiley-Liss, Inc.