BACKGROUND: To examine the relationship between autism spectrum disorders (ASD) and specific language impairment (SLI), family studies typically take a comparative approach where families with one disease are examined for traits of the other disease. In contrast, the present report is the first study with both disorders required to be present in each family to provide a more direct test of the hypothesis of shared genetic etiology. METHODS: We behaviorally assessed 51 families including at least one person with ASD and at least one person with SLI (without ASD). Pedigree members were tested with 22 standardized measures of language and intelligence. Because these extended families include a nonshared environmental contrast, we calculated heritability, not just familiality, for each measure twice: 1) baseline heritability analysis, compared with; 2) heritability estimates after statistically removing ASD subjects from pedigrees. RESULTS: Significant increases in heritability on four supra-linguistic measures (including Pragmatic Judgment) and a composite language score but not on any other measures were observed when removing ASD subjects from the analysis, indicating differential genetic effects that are unique to ASD. Nongenetic explanations such as effects of ASD severity or measurement error or low score variability in ASD subjects were systematically ruled out, leaving the hypothesis of nonadditive genetics effects as the potential source of the heritability change caused by ASD. CONCLUSIONS: Although the data suggest genetic risk factors common to both SLI and ASD, there are effects that seem unique to ASD, possibly caused by nonadditive gene-gene interactions of shared risk loci.
BACKGROUND: To examine the relationship between autism spectrum disorders (ASD) and specific language impairment (SLI), family studies typically take a comparative approach where families with one disease are examined for traits of the other disease. In contrast, the present report is the first study with both disorders required to be present in each family to provide a more direct test of the hypothesis of shared genetic etiology. METHODS: We behaviorally assessed 51 families including at least one person with ASD and at least one person with SLI (without ASD). Pedigree members were tested with 22 standardized measures of language and intelligence. Because these extended families include a nonshared environmental contrast, we calculated heritability, not just familiality, for each measure twice: 1) baseline heritability analysis, compared with; 2) heritability estimates after statistically removing ASD subjects from pedigrees. RESULTS: Significant increases in heritability on four supra-linguistic measures (including Pragmatic Judgment) and a composite language score but not on any other measures were observed when removing ASD subjects from the analysis, indicating differential genetic effects that are unique to ASD. Nongenetic explanations such as effects of ASD severity or measurement error or low score variability in ASD subjects were systematically ruled out, leaving the hypothesis of nonadditive genetics effects as the potential source of the heritability change caused by ASD. CONCLUSIONS: Although the data suggest genetic risk factors common to both SLI and ASD, there are effects that seem unique to ASD, possibly caused by nonadditive gene-gene interactions of shared risk loci.
Authors: Joachim Hallmayer; Sue Cleveland; Andrea Torres; Jennifer Phillips; Brianne Cohen; Tiffany Torigoe; Janet Miller; Angie Fedele; Jack Collins; Karen Smith; Linda Lotspeich; Lisa A Croen; Sally Ozonoff; Clara Lajonchere; Judith K Grether; Neil Risch Journal: Arch Gen Psychiatry Date: 2011-07-04
Authors: Maricela Alarcón; Brett S Abrahams; Jennifer L Stone; Jacqueline A Duvall; Julia V Perederiy; Jamee M Bomar; Jonathan Sebat; Michael Wigler; Christa L Martin; David H Ledbetter; Stanley F Nelson; Rita M Cantor; Daniel H Geschwind Journal: Am J Hum Genet Date: 2008-01 Impact factor: 11.025
Authors: Anne Gregor; Beate Albrecht; Ingrid Bader; Emilia K Bijlsma; Arif B Ekici; Hartmut Engels; Karl Hackmann; Denise Horn; Juliane Hoyer; Jakub Klapecki; Jürgen Kohlhase; Isabelle Maystadt; Sandra Nagl; Eva Prott; Sigrid Tinschert; Reinhard Ullmann; Eva Wohlleber; Geoffrey Woods; André Reis; Anita Rauch; Christiane Zweier Journal: BMC Med Genet Date: 2011-08-09 Impact factor: 2.103
Authors: Christopher W Bartlett; Liping Hou; Judy F Flax; Abby Hare; Soo Yeon Cheong; Zena Fermano; Barbie Zimmerman-Bier; Charles Cartwright; Marco A Azaro; Steven Buyske; Linda M Brzustowicz Journal: Am J Psychiatry Date: 2014-01 Impact factor: 18.112
Authors: Matthew Bruni; Judy F Flax; Steven Buyske; Amber D Shindhelm; Caroline Witton; Linda M Brzustowicz; Christopher W Bartlett Journal: Behav Genet Date: 2016-11-09 Impact factor: 2.805
Authors: N Marrus; L P Hall; S J Paterson; J T Elison; J J Wolff; M R Swanson; J Parish-Morris; A T Eggebrecht; J R Pruett; H C Hazlett; L Zwaigenbaum; S Dager; A M Estes; R T Schultz; K N Botteron; J Piven; J N Constantino Journal: J Neurodev Disord Date: 2018-10-22 Impact factor: 4.025