title: Parental social responsiveness and risk of autism spectrum disorder in offspring.
abstract: OBJECTIVE
  Although autism spectrum disorder (ASD) is known to be heritable, patterns of inheritance of subclinical autistic traits in nonclinical samples are poorly understood.
  
  
  OBJECTIVE
  To examine the familiality of Social Responsiveness Scale (SRS) scores of individuals with and without ASD.
  
  
  METHODS
  We performed a nested case-control study (pilot study: July 1, 2007, through June 30, 2009; full-scale study: September 15, 2008, through September 14, 2012) within a population-based longitudinal cohort. Participants were drawn from the Nurses' Health Study II, a cohort of 116,430 female nurses recruited in 1989. Case participants were index children with reported ASD; control participants were frequency matched by year of birth of case participants among those not reporting ASD. Of 3161 eligible participants, 2144 nurses (67.8%) returned SRS forms for a child and at least 1 parent and were included in these analyses.
  
  
  METHODS
  The SRS scores, as reported by nurse mothers and their spouses, were examined in association with risk of ASD using crude and adjusted logistic regression analyses. The SRS scores of the children were examined in association with SRS scores of the parents using crude and adjusted linear regression analyses stratified by case status.
  
  
  METHODS
  Autism spectrum disorder, assessed by maternal report, validated in a subgroup with the Autism Diagnostic Interview-Revised.
  
  
  RESULTS
  A total of 1649 individuals were included in these analyses, including 256 ASD case participants, 1393 control participants, 1233 mothers, and 1614 fathers. Risk of ASD was increased by 85.0% among children whose parents had concordantly elevated SRS scores (odds ratio [OR], 1.85; 95% CI, 1.08-3.16) and by 52.0% when the score of either parent was elevated (OR, 1.52; 95% CI, 1.11-2.06). Elevated scores of the father significantly increased the risk of ASD in the child (OR, 1.94; 95% CI, 1.38-2.71), but no association was seen with elevated scores of the mother. Elevated parent scores significantly increased child scores in controls, corresponding to an increase in 23 points (P < .001).
  
  
  CONCLUSIONS
  These findings support the role of additive genetic influences in concentrating inherited ASD susceptibility in successive generations and the potential role of preferential mating, and suggest that typical variation in parental social functioning can produce clinically significant differences in offspring social traits.
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts2Department of Public Health Sciences, University of California, Davis.
authors.forename: Kristen
authors.initials: K
authors.lastname: Lyall
authors.affiliation: Department of Psychiatry, Washington University, St Louis, Missouri.
authors.forename: John N
authors.initials: JN
authors.lastname: Constantino
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts5Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Weisskopf
authors.affiliation: Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Roberts
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts4Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts7Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ascherio
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts8Department of Psychiatry, Maine Medical Center/Maine Medical Center Research Institute, Portland.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Santangelo
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000453:epidemiology / Q000235:genetics*; D002675:Child, Preschool; D005220:Fathers / Q000523:psychology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009035:Mothers / Q000523:psychology*; D011569:Psychiatric Status Rating Scales; D011897:Random Allocation; D012306:Risk; D012737:Sex Factors; D012919:Social Behavior; D014481:United States / Q000453:epidemiology; D055815:Young Adult
references.citation: J Autism Dev Disord. 2012 Feb;42(2):294-300
references.pmid: 21516433
references.citation: Am J Psychiatry. 2006 Feb;163(2):294-6
references.pmid: 16449484
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2009 Apr 5;150B(3):328-34
references.pmid: 18618672
references.citation: Autism. 2013 Jan;17(1):15-26
references.pmid: 22399449
references.citation: Res Dev Disabil. 2012 May-Jun;33(3):944-50
references.pmid: 22277583
references.citation: J Child Psychol Psychiatry. 2013 Feb;54(2):216-24
references.pmid: 22823182
references.citation: J Am Acad Child Adolesc Psychiatry. 2012 Aug;51(8):756-8
references.pmid: 22840545
references.citation: Biol Psychiatry. 2005 Mar 15;57(6):655-60
references.pmid: 15780853
references.citation: J Autism Dev Disord. 1994 Oct;24(5):659-85
references.pmid: 7814313
references.citation: JAMA. 1997 Oct 1;278(13):1078-83
references.pmid: 9315766
references.citation: JAMA Pediatr. 2013 Oct;167(10):947-53
references.pmid: 23959427
references.citation: Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5258-62
references.pmid: 23431162
references.citation: J Autism Dev Disord. 2012 Sep;42(9):1998-9
references.pmid: 22183423
references.citation: J Autism Dev Disord. 2003 Aug;33(4):427-33
references.pmid: 12959421
references.citation: J Child Psychol Psychiatry. 2004 May;45(4):719-26
references.pmid: 15056304
references.citation: J Autism Dev Disord. 2012 Nov;42(11):2450-9
references.pmid: 22407579
references.citation: Am J Psychiatry. 2010 Nov;167(11):1349-56
references.pmid: 20889652
references.citation: Arch Gen Psychiatry. 2011 Nov;68(11):1095-102
references.pmid: 21727249
references.citation: J Autism Dev Disord. 2012 Nov;42(11):2431-9
references.pmid: 22422339
references.citation: J Child Psychol Psychiatry. 2007 May;48(5):464-72
references.pmid: 17501727
references.citation: Mol Psychiatry. 2013 Feb;18(2):137-8
references.pmid: 22371046
references.citation: J Autism Dev Disord. 2005 Feb;35(1):129-33
references.pmid: 15796128
references.citation: Autism. 2013 Nov;17(6):736-42
references.pmid: 22914777
references.citation: Arch Gen Psychiatry. 2011 Nov;68(11):1113-21
references.pmid: 22065527
references.citation: Stat Med. 1991 Apr;10(4):585-98
references.pmid: 2057657
references.citation: J Child Psychol Psychiatry. 2010 Sep;51(9):1021-30
references.pmid: 20546079
references.citation: Arch Gen Psychiatry. 2003 May;60(5):524-30
references.pmid: 12742874
references.citation: Autism. 2012 May;16(3):247-60
references.pmid: 21949002
references.citation: Dev Psychopathol. 2009 Winter;21(1):127-38
references.pmid: 19144226
references.citation: Paediatr Perinat Epidemiol. 2012 Jul;26(4):361-72
references.pmid: 22686388