Advertisement

Evidence of Assortative Mating in Autism Spectrum Disorder

  • Siobhan Connolly
    Correspondence
    Address correspondence to Siobhan Connolly, Ph.D., Computer Science and Mathematics Dept., Dundalk Institute of Technology, Marshes Upper, Dundalk, Co. Louth, A91 K584, Ireland.
    Affiliations
    Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences, Dublin, Ireland

    Computer Science and Mathematics Department, Dundalk Institute of Technology, Dundalk, Ireland
    Search for articles by this author
  • Richard Anney
    Affiliations
    Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences, Dublin, Ireland

    Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University School of Medicine, Cathays, Cardiff, United Kingdom
    Search for articles by this author
  • Louise Gallagher
    Affiliations
    Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences, Dublin, Ireland
    Search for articles by this author
  • Elizabeth A. Heron
    Affiliations
    Neuropsychiatric Genetics Research Group, Department of Psychiatry, Trinity College Dublin, Trinity Centre for Health Sciences, Dublin, Ireland
    Search for articles by this author

      Abstract

      Background

      Assortative mating is a nonrandom mating system in which individuals with similar genotypes and/or phenotypes mate with one another more frequently than would be expected in a random mating system. Assortative mating has been hypothesized to play a role in autism spectrum disorder (ASD) in an attempt to explain some of the increase in the prevalence of ASD that has recently been observed. ASD is considered to be a heritable neurodevelopmental disorder, but there is limited understanding of its causes. Assortative mating can be explored through both phenotypic and genotypic data, but up until now it has never been investigated through genotypic measures in ASD.

      Methods

      We investigated genotypically similar mating pairs using genome-wide single nucleotide polymorphism data on trio families (Autism Genome Project data [1590 parents] and Simons Simplex Collection data [1962 parents]). To determine whether or not an excess in genetic similarity was present, we employed kinship coefficients and examined spousal correlation between the principal components in both the Autism Genome Project and Simons Simplex Collection datasets. We also examined assortative mating using phenotype data on the parents to detect any correlation between ASD traits.

      Results

      We found significant evidence of genetic similarity between the parents of ASD offspring using both methods in the Autism Genome Project dataset. In the Simons Simplex Collection, there was also significant evidence of genetic similarity between the parents when explored through spousal correlation.

      Conclusions

      This study gives further support to the hypothesis that positive assortative mating plays a role in ASD.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Schneider K.A.
        • Peischl S.
        Evolution of assortative mating in a population expressing dominance.
        PLoS One. 2011; 6: e16821
        • De S.
        • Pal S.K.
        • Ghosh A.
        Genotypic and phenotypic assortative mating in genetic algorithm.
        Inf Sci. 1998; 105: 209-226
        • Sebro R.
        • Hoffman T.J.
        • Lange C.
        • Rogus J.J.
        • Risch N.J.
        Testing for non-random mating: Evidence for ancestry-related assortative mating in the Framingham Heart Study.
        Genet Epidemiol. 2010; 34: 674-679
        • Génin E.
        • Ober C.
        • Weitkamp L.
        • Thomson G.
        A robust test for assortative mating.
        Eur J Hum Genet. 2000; 8: 119-124
        • Domingue B.W.
        • Fletcher J.
        • Conley D.
        • Boardman J.D.
        Genetic and educational assortative mating among US adults.
        Proc Natl Acad Sci U S A. 2014; 111: 7996-8000
        • Conley D.
        • Laidley T.
        • Belsky D.W.
        • Fletcher J.M.
        • Boardman J.D.
        • Domingue B.W.
        Assortative mating and differential fertility by phenotype and genotype across the 20th century.
        Proc Natl Acad Sci U S A. 2016; 113: 6647-6652
        • Robinson M.R.
        • Kleinman A.
        • Graff M.
        • Vinkhuyzen A.A.E.
        • Couper D.
        • Miller M.B.
        • et al.
        Genetic evidence of assortative mating in humans.
        Nat Hum Behav. 2017; 1: 0016
        • Yengo L.
        • Robinson M.R.
        • Keller M.C.
        • Kemper K.E.
        • Yang Y.
        • Trzaskowski M.
        • et al.
        Imprint of assortative mating on the human genome.
        Nat Hum Behav. 2018; 2: 948-954
        • Gaugler T.
        • Klei L.
        • Sanders S.J.
        • Bodea C.A.
        • Goldberg A.P.
        • Lee A.B.
        • et al.
        Most genetic risk for autism resides with common variation.
        Nat Genet. 2014; 46: 881-885
        • Baron-Cohen S.
        Two new theories of autism: Hyper-systemising and assortative mating.
        Archives Dis Child. 2006; 91: 2-5
        • Williams J.G.
        • Higgins J.P.T.
        • Brayne C.E.G.
        Systematic review of prevalence studies of autism spectrum disorders.
        Arch Dis Child. 2006; 91: 8-15
        • Harrison M.J.
        • O’Hare A.E.
        • Campbell H.
        • Adamson A.
        • McNeillage J.
        Prevalence of autistic spectrum disorders in Lothian, Scotland: An estimate using the “capture–recapture” technique.
        Arch Dis Child. 2006; 91: 16-19
        • Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators, Centers for Disease Control and Prevention
        Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008.
        MMWR Surveill Summ. 2012; 61: 1-19
        • Peyrot W.J.
        • Robinson M.R.
        • Penninx B.W.J.H.
        • Wray N.R.
        Exploring boundaries for the genetic consequences of assortative mating for psychiatric traits.
        JAMA Psychiatry. 2016; 73: 1189-1195
        • Baron-Cohen S.
        • Hammer J.
        Parents of children with Asperger syndrome: What is the cognitive phenotype?.
        J Cogn Neurosci. 1997; 9: 548-554
        • Silberman S.
        The geek syndrome. Wired 9.
        2001
        • Baron-Cohen S.
        • Wheelwright S.
        • Burtenshaw A.
        • Hobson E.
        Mathematical talent is linked to autism.
        Hum Nat. 2007; 18: 125-131
        • Roelfsema M.T.
        • Hoekstra R.A.
        • Allison C.
        • Wheelwright S.
        • Brayne C.
        • Matthews F.E.
        • Baron-Cohen S.
        Are autism spectrum conditions more prevalent in an information technology region? A school-based study of three regions in The Netherlands.
        J Autism Dev Disord. 2012; 42: 734-739
        • Dickerson A.S.
        • Pearson D.A.
        • Loveland K.A.
        • Rahbar M.H.
        • Filipek P.A.
        Role of parental occupation in autism spectrum disorder diagnosis and severity.
        Res Autism Spectr Disord. 2014; 8: 997-1007
        • Warrier V.
        • Toro R.
        • Chakrabarti B.
        • Børglum A.D.
        • Grove J.
        • et al.
        • the iPSYCH-Broad Autism Group
        Systemizing is genetically correlated with autism and is genetically distinct from social autistic traits.
        bioRxiv. 2017; ([published online ahead of print Dec 3])
        • Nordsletten A.E.
        • Larsson H.
        • Crowley J.J.
        • Almqvist C.
        • Lichtenstein P.
        • Mataix-Cols D.
        Patterns of nonrandom mating within and across 11 major psychiatric disorders.
        JAMA Psychiatry. 2016; 73: 354-361
        • Baron-Cohen S.
        The hyper-systemizing, assortative mating theory of autism.
        Prog Neuropsychopharmacol Biol Psychiatry. 2006; 30: 865-872
        • Happé F.
        • Briskman J.
        • Frith U.
        Exploring the cognitive phenotype of autism: weak “central coherence” in parents and siblings of children with autism: II. Real-life skills and preferences.
        J Child Psychol Psychiatry. 2001; 42: 309-316
        • Constantino J.N.
        • Todd R.D.
        Intergenerational transmission of subthreshold autistic traits in the general population.
        Biol Psychiatry. 2005; 57: 655-660
        • Lyall K.
        • Constantino J.N.
        • Weisskopf M.G.
        • Roberts A.L.
        • Ascherio A.
        • Santangelo S.L.
        Parental social responsiveness and risk of autism spectrum disorder in offspring.
        JAMA Psychiatry. 2014; 71: 936-942
        • Gerdts J.A.
        • Bernier R.
        • Dawson G.
        • Estes A.
        The broader autism phenotype in simplex and multiplex families.
        J Autism Dev Disord. 2013; 43: 1597-1605
        • Virkud Y.V.
        • Todd R.D.
        • Abbacchi A.M.
        • Zhang Y.
        • Constantino J.N.
        Familial aggregation of quantitative autistic traits in multiplex versus simplex autism.
        Am J Med Genet B Neuropsychiatr Genet. 2009; 150B: 328-334
        • Page J.
        • Constantino J.N.
        • Zambrana K.
        • Martin E.
        • Tunc I.
        • Zhang Y.
        • et al.
        Quantitative autistic trait measurements index background genetic risk for ASD in Hispanic families.
        Mol Autism. 2016; 7: 39
        • Rubenstein E.
        • Chawla D.
        Broader autism phenotype in parents of children with autism: A systematic review of percentage estimates.
        J Child Fam Stud. 2018; 27: 1705-1720
        • Browning S.R.
        • Browning B.L.
        Population structure can inflate SNP-based heritability estimates.
        Am J Hum Genet. 2011; 89: 191-193
        • Sebro R.
        • Risch N.J.
        A brief note on the resemblance between relatives in the presence of population stratification.
        Heredity. 2012; 108: 563-568
        • Sebro R.
        • Peloso G.M.
        • Dupuis J.
        • Risch N.J.
        • Freedman M.
        • Groop L.
        • et al.
        Structured mating: Patterns and implications.
        PLoS Genet. 2017; 13: e1006655
        • Klei L.
        • Sanders S.J.
        • Murtha M.T.
        • Hus V.
        • Lowe J.K.
        • Willsey A.J.
        • et al.
        Common genetic variants, acting additively, are a major source of risk for autism.
        Mol Autism. 2012; 3: 9
        • Brosnan M.
        • Walker I.
        A preliminary investigation into the potential role of waist hip ratio (WHR) preference within the assortative mating hypothesis of autistic spectrum disorders.
        J Autism Dev Disord. 2009; 39: 164-171
        • Zhu Z.
        • Lu X.
        • Yuan D.
        • Huang S.
        Close genetic relationships between a spousal pair with autism-affected children and high minor allele content in cases in autism-associated SNPs.
        Genomics. 2017; 109: 9-15
        • Anney R.
        • Klei L.
        • Pinto D.
        • Regan R.
        • Conroy J.
        • Magalhaes T.R.
        • et al.
        A genome-wide scan for common alleles affecting risk for autism.
        Hum Mol Genet. 2010; 19: 4072-4082
        • Anney R.
        • Klei L.
        • Pinto D.
        • Almeida J.
        • Bacchelli E.
        • Baird G.
        • et al.
        Individual common variants exert weak effects on the risk for autism spectrum disorders.
        Hum Mol Genet. 2012; 21: 4781-4792
        • Fischbach G.D.
        • Lord C.
        The Simons Simplex Collection: A resource for identification of autism genetic risk factors.
        Neuron. 2010; 68: 192-195
        • Sanders S.J.
        • Ercan-Sencicek G.A.
        • Hus V.
        • Luo R.
        • Murtha M.T.
        • Moreno-De Luca D.
        • et al.
        Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism.
        Neuron. 2011; 70: 863-885
        • Chaste P.
        • Klei L.
        • Sanders S.J.
        • Hus V.
        • Murtha M.T.
        • Lowe J.K.
        • et al.
        A genomewide association study of autism using the Simons Simplex Collection: Does reducing phenotypic heterogeneity in autism increase genetic homogeneity?.
        Biol Psychiatry. 2015; 77: 775-784
        • Lord C.
        • Rutter M.
        • Le Couteur A.
        Autism Diagnostic Interview–Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders.
        J Autism Dev Disord. 1994; 24: 659-685
        • Lord C.
        • Risi S.
        • Lambrecht L.
        • Cook E.H.
        • Leventhal B.L.
        • DiLavore P.C.
        • et al.
        The Autism Diagnostic Observation Schedule–Generic: A standard measure of social and communication deficits associated with the spectrum of autism.
        J Autism Dev Disord Biol Psychiatry. 2000; 30: 205-223
        • Geschwind D.H.
        • Sowinski J.
        • Lord C.
        • Iversen P.
        • Shestack J.
        • Jones P.
        • et al.
        The Autism Genetic Resource Exchange: A resource for the study of autism and related neuropsychiatric conditions.
        Am J Hum Genet. 2001; 69: 463-466
        • Waltes R.
        • Gfesser J.
        • Haslinger D.
        • Schneider-Momm K.
        • Biscaldi M.
        • Voran A.
        • et al.
        Common EIF4E variants modulate risk for autism spectrum disorders in the high-functioning range.
        J Neural Transm (Vienna). 2014; 121: 1107-1116
        • Price A.L.
        • Weale M.E.
        • Patterson N.
        • Myers S.R.
        • Need A.C.
        • Shianna K.V.
        • et al.
        Long-range LD can confound genome scans in admixed populations.
        Am J Hum Genet. 2008; 83 (author reply 135–139): 132-135
        • Abdellaoui A.
        • Verweij K.J.H.
        • Zietsch B.P.
        No evidence for genetic assortative mating beyond that due to population stratification.
        Proc Natl Acad Sci U S A. 2014; 111: E4137
        • Alexander D.H.
        • Novembre J.
        • Lange K.
        Fast model-based estimation of ancestry in unrelated individuals.
        Genome Res. 2009; 19: 1655-1664
        • Altshuler D.M.
        • Gibbs R.A.
        • Peltonen L.
        • Dermitzakis E.
        • Schaffner S.F.
        • Yu F.
        • et al.
        Integrating common and rare genetic variation in diverse human populations.
        Nature. 2010; 467: 52-58
        • Stevens E.L.
        • Baugher J.D.
        • Shirley M.D.
        • Frelin L.P.
        • Pevsner J.
        Unexpected relationships and inbreeding in HapMap phase III populations.
        PLoS One. 2012; 7: e49575
        • Manichaikul A.
        • Mychaleckyj J.C.
        • Rich S.S.
        • Daly K.
        • Sale M.
        • Chen W.M.
        Robust relationship inference in genome-wide association studies.
        Bioinformatics. 2010; 26: 2867-2873
        • International HapMap Consortium
        The International HapMap Project.
        Nature. 2003; 426: 789-796
        • Lee S.
        • Epstein M.P.
        • Duncan R.
        • Lin X.
        Sparse principal component analysis for identifying ancestry-informative markers in genome-wide association studies.
        Genet Epidemiol. 2012; 36: 293-302
        • Price A.L.
        • Patterson N.J.
        • Plenge R.M.
        • Weinblatt M.E.
        • Shadick N.A.
        • Reich D.
        Principal components analysis corrects for stratification in genome-wide association studies.
        Nat Genet. 2006; 38: 904-909
        • Hurley R.S.E.
        • Losh M.
        • Parlier M.
        • Reznick J.S.
        • Piven J.
        The Broad Autism Phenotype Questionnaire.
        J Autism Dev Disord. 2007; 37: 1679-1690
        • Constantino J.N.
        • Gruber C.P.
        The Social Responsiveness Scale Manual.
        Western Psychological Services, Los Angeles2005
        • Abdellaoui A.
        • Hottenga J.J.
        • de Knijff P.
        • Nivard M.G.
        • Xiao X.
        • Scheet P.
        • et al.
        Population structure, migration, and diversifying selection in The Netherlands.
        Eur J Hum Genet. 2013; 21: 1277-1285
        • Bernier R.
        • Gerdts J.
        • Munson J.
        • Dawson G.
        • Estes A.
        Evidence for broader autism phenotype characteristics in parents from multiple-incidence autism families.
        Autism Res. 2012; 5: 13-20
        • Chaste P.
        • Leboyer M.
        Autism risk factors: Genes, environment, and gene–environment interactions.
        Dialogues Clin Neurosci. 2012; 14: 281-292
        • Anney R.J.L.
        • Ripke S.
        • Anttila V.
        • Grove J.
        • Holmans P.
        • et al.
        • Autism Spectrum Disorders Working Group of the Psychiatric Genomics Consortium
        Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.
        Mol Autism. 2017; 8: 21

      Linked Article

      • Assortative Mating in Autism Spectrum Disorder: Toward an Evidence Base From DNA Data, but Not There Yet
        Biological PsychiatryVol. 86Issue 4
        • Preview
          The term “assortative mating” always seems a bit distasteful when applied to humans, but it is the most succinct way to convey the concept of the consequences in children (and their descendants) associated with a consistent trend of phenotypic similarities between parents of heritable traits. Almost all phenotypes have some genetic contribution, and therefore children have trait values correlated with those of their parents. There are so many dimensions on which partner choice can be made that the genetic structure within future generations is not necessarily affected (Figure 1).
        • Full-Text
        • PDF