Autism and Acquired Misapprehensions about Heritability

A minimal requirement for evolution via natural selection is heritable phenotypic variation that affects reproductive success, or more generally, genetic success.  The concept of heritability is often used somewhat loosely in casual non-technical conversation, but there is also a precise technical definition – actually there are two widely-employed technical definitions, each of which is characterized below.

Consideration of the meaning and usefulness of heritability is prompted by the publication of a new study (Hallmayer et al., 2011) addressing the relative contributions of genetic and environmental variation in the origins of autism. Previous studies, of modest size, had led to the conclusion that the heritability of autism-related phenotypes was about 90%.  In contrast, the new somewhat larger study (192 pairs of monozygotic and dizygotic twins) finds that the heritability values for both autism and so-called autism spectrum disorders (ASD) were between 35 and 40%.

In the technical, scientific context heritability is the proportion of phentotypic variation that is attributable to genetic variation.  This concept has practical value for animal and plant breeders who can estimate the extent of response to selection for a given trait by knowing the heritability for that trait.  The form of heritability of primary interest in this application is concerned solely with the additive genetic variance and is known as heritability in the narrow sense.

In contrast, investigators in the fields of human behavioral genetics, psychiatry, and psychology, who are interested in the extent to which human behavioral traits are heritable, tend to use the definition of heritability in the broad sense.  This definition takes account of genetic variance from all sources including dominance and epistasis, sources that are not of prime interest for animal and plant breeding.

Richard Lewontin, an eminent population geneticist and among the foremost critics of using heritability values in the context of exploring human behavioral abnormalities has suggested that there are formidable obstacles to accurately separating genetic from environmental variation in accounting for phenotypic variation.  According to Lewontin, the chief issue is that the genetic variance contributing to phenotypic variance on the basis of gene-gene interactions, gene-environment interactions, and non-random correlations between particular alleles and particular environments is often substantial (Downes, 2004).  In the study by Hallmayer et al., the authors intentionally ignored gene-environment interactions (and probably gene-environment correlations), although they claim that if such interactions were important, then the heritability estimates would be even lower.

In any case, individuals attempting to interpret studies pertaining to the contribution of genetic variation to human behavioral variation should be cognizant of the fact that a heritability value is a property of a population associated with a particular set of environmental factors (which can be exceedingly difficult to define and specify in the human situation) and with a particular set of allele frequency distributions (that, of course, can change) at an ensemble of loci.  A value for hertitability is not: 1) a property of a gene, a trait, or even a gene-trait pair, 2) a quantity that meaningfully applies to any given individual, 3) a quantitative indication of “how much of a trait is due to genetics” in a colloquial sense, or 4) a quantitative indication of the potential for environmental intervention to alter a trait of interest.  Thus, the results of Hallmeyer et al. do not mean, as asserted by the author (Tarkan, 2011) of a New York Times article on the study, that “only 38 percent of the cases could be attributed to genetic factors …” Every case involves the interplay of genetic and environmental factors.  Furthermore, even traits that are “100% heritable” are not necessarily impervious to the effects of environmental alterations (e.g., medical interventions).

The authors of the study suggest that because of the reduced value for the heritability of autism or ASD (relative to previous studies), there is greater reason to search for environmental factors that contribute to the etiology and pathogenesis of these conditions.  However, since the concordance rate for autism or ASD has not been 100% in any study, it was already reasonable to infer that genetic factors cannot solely account for the occurrence of the condition in any given individual.  Furthermore, the recent dramatic increase in apparent incidence of autism-related diagnoses (whatever subsequent research ultimately reveals about the mix of contributing factors) provides an independent reason to at least consider environmental factors in causally contributing to autism.

Meanwhile evidence is accumulating for the substantial influence of many different genetic polymorphisms that influence aspects of neuron biology, such as synaptic function, on the pathogenesis of autism and autism-related disorders (Herbert, 2011).    A recent article by Betancur (2011) documents more than 100 genetic polymorphisms and other genomic variations associated with autism or with ASD.  This author concludes that the etiology of autism and ASD is highly genetically heterogeneous.

The best default assumption is that any given phenotype arises through interactions between genetic and environmental factors (Moore, 2002).  Therefore, irrespective of the value for the heritability of autism or ASD, researchers should continue to explore both genetic and environmental factors that may be contributing to the etiology and pathogenesis of these conditions.

References

Hallmayer J, Cleveland S, Torres A, Phillips J, Cohen B, Torigoe T, Miller J, Fedele A, Collins J, Smith K, Lotspeich L, Croen LA, Ozonoff S, Lajonchere C, Grether JK, Risch N. Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism. Arch Gen Psychiatry. 2011 Jul 4. [Epub  ahead of print] PubMed PMID: 21727249.

Downes, Stephen M., “Heredity and Heritability”, The Stanford Encyclopedia of Philosophy (Fall 2004 Edition), Edward N. Zalta (ed.), URL = <http://plato.stanford.edu/archives/fall2004/entries/heredity/>.

Tarkan, Laurie. New study implicates environmental factors in autism. New York Times, July 4, 2011. http://www.nytimes.com/2011/07/05/health/research/05autism.html?_r=1&ref=health.

Herbert, MR. SHANK 3, the synapse, and autism. N Engl J Med. 2011 Jul 14;365(2):173-5. PubMed PMID: 21751912.

Betancur C. Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res. 2011 Mar 22;1380:42-77. Epub 2010 Dec 1. PubMed PMID: 21129364.

Moore, David S. The Dependent Gene: The Fallacy of Nature vs. Nurture. W. H. Freeman & Co., 2002.