TY - JOUR
T1 - Familial aggregation of quantitative autistic traits in multiplex versus simplex autism
AU - Virkud, Yamini V.
AU - Todd, Richard D.
AU - Abbacchi, Anna M.
AU - Zhang, Yi
AU - Constantino, John N.
PY - 2009/4/5
Y1 - 2009/4/5
N2 - 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.
AB - 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.
KW - Complex disease
KW - Endophenotype
KW - Family studies
KW - Genetics
KW - Pervasive developmental disorders
KW - Social responsiveness scale
UR - http://www.scopus.com/inward/record.url?scp=63449088785&partnerID=8YFLogxK
U2 - 10.1002/ajmg.b.30810
DO - 10.1002/ajmg.b.30810
M3 - Article
C2 - 18618672
AN - SCOPUS:63449088785
SN - 1552-4841
VL - 150
SP - 328
EP - 334
JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
IS - 3
ER -