Minor physical anomalies in autism: a meta-analysis.
ABSTRACT Autism is a complex neurodevelopmental disorder in which the interactions of genetic, epigenetic and environmental influences play a causal role. Despite the compelling evidence for a strong heritability, the etiology and molecular mechanisms underlying autism remain unclear. High phenotypic variability and genetic heterogeneity confounds the identification of susceptibility genes. The lack of robust indicators to tackle this complexity in autism has led researchers to seek for novel diagnostic tools to create homogenous subgroups. Several studies have indicated that patients with autism have higher rates of minor physical anomalies (MPAs) and that MPAs may serve as a diagnostic tool; however, the results have been inconsistent. Using the cumulative data from seven studies on MPAs in autism, this meta-analysis seeks to examine whether the aggregate data provide evidence of a large mean effect size and statistical significance for MPAs in autism. It covers the studies using multiple research methods till June 2007. The current results from seven studies suggested a significant association of MPAs in autism with a robust pooled effect size (d=0.84), and thereby provide the strongest evidence to date about the close association between MPAs and autism. Our results emphasize the importance of MPAs in the identification of heterogeneity in autism and suggest that the success of future autism genetics research will be exploited by the use of MPAs. Implications for the design of future studies on MPAs in autism are discussed and suggestions for further investigation of these important markers are proposed. Clarifying this relation might improve understanding of risk factors and molecular mechanisms in autism.
SourceAvailable from: Izzet Duyar[Show abstract] [Hide abstract]
ABSTRACT: While consanguineous marriage has been shown to result in a small increase in risk of recessive Mendelian disorders among offspring, far less research has been conducted on the effects of inbreeding on complex traits. These effects, thought to result from increased developmental instability due to loss of heterozygosity, are expected to be found more pervasively than rare recessive Mendelian traits and are expected to result in increased developmental noise. Here, we test for a direct effect of inbreeding on 2D : 4D, a putative indicator of prenatal hormonal environment. We compared the 2D : 4D ratios of 122 male and 108 female consanguineous (children of first cousin marriages) high school and university students to those of 142 male and 122 females controls. Across hands and sex, consanguineous parentage was consistently associated with lower, more masculine-typical, digit ratios. Digit ratios were 1.3-1.9 times more variable among the consanguineous group than the control group. While socio-economic status cannot explain the effects seen in our data, we found that lower, more masculinized, digit ratios were associated with lower family income. Our results suggest that consanguineous marriages are associated with a fetal environment that influences morphological development and may have associated behavioral sequelae. Am. J. Hum. Biol., 2013. © 2013 Wiley Periodicals, Inc.American Journal of Human Biology 03/2014; 26(2). DOI:10.1002/ajhb.22491 · 1.93 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Minor physical anomalies (MPAs) are slight structural aberrations indicative of abnormal neurodevelopment. Most studies of MPAs in bipolar disorder have yielded limited results. We attempted to assess the potential value of MPAs as a classifying test in the status bipolar I patients vs. normal controls. Sixty one bipolar I patients and 103 controls were evaluated for MPAs using a slightly modified version of the Waldrop scale. The specificity, sensitivity and predictive value of different total MPA (MPA-T) scores were determined. The cut-off MPA-T scores that optimally discriminated patients from controls (exhibiting the most balanced sets of sensitivity, specificity, positive and negative predictive values) were MPA-T≥4 and MPA-T≥5. These values set a "border zone" in which bipolar I patients began to prevail significantly over controls. The latter presented most frequently with MPA-T ≤3 and rarely with MPA-T ≥6. Bipolar I patients prevailed among outliers (subjects with significantly higher MPA-T scores). Our data establish MPA-T score as a reliable index in distinguishing between bipolar I patients and normal controls and are consistent with the hypothesis of abnormal neurodevelopment in bipolar disorder.Psychiatry Research 07/2013; DOI:10.1016/j.psychres.2013.06.026 · 2.68 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Many factors affect the risks for neurodevelopmental maladies such as autism spectrum disorders (ASD) and intellectual disability (ID). To compare environmental, phenotypic, socioeconomic and state-policy factors in a unified geospatial framework, we analyzed the spatial incidence patterns of ASD and ID using an insurance claims dataset covering nearly one third of the US population. Following epidemiologic evidence, we used the rate of congenital malformations of the reproductive system as a surrogate for environmental exposure of parents to unmeasured developmental risk factors, including toxins. Adjusted for gender, ethnic, socioeconomic, and geopolitical factors, the ASD incidence rates were strongly linked to population-normalized rates of congenital malformations of the reproductive system in males (an increase in ASD incidence by 283% for every percent increase in incidence of malformations, 95% CI: [91%, 576%], p<6×10-5). Such congenital malformations were barely significant for ID (94% increase, 95% CI: [1%, 250%], p = 0.0384). Other congenital malformations in males (excluding those affecting the reproductive system) appeared to significantly affect both phenotypes: 31.8% ASD rate increase (CI: [12%, 52%], p<6×10-5), and 43% ID rate increase (CI: [23%, 67%], p<6×10-5). Furthermore, the state-mandated rigor of diagnosis of ASD by a pediatrician or clinician for consideration in the special education system was predictive of a considerable decrease in ASD and ID incidence rates (98.6%, CI: [28%, 99.99%], p = 0.02475 and 99% CI: [68%, 99.99%], p = 0.00637 respectively). Thus, the observed spatial variability of both ID and ASD rates is associated with environmental and state-level regulatory factors; the magnitude of influence of compound environmental predictors was approximately three times greater than that of state-level incentives. The estimated county-level random effects exhibited marked spatial clustering, strongly indicating existence of as yet unidentified localized factors driving apparent disease incidence. Finally, we found that the rates of ASD and ID at the county level were weakly but significantly correlated (Pearson product-moment correlation 0.0589, p = 0.00101), while for females the correlation was much stronger (0.197, p<2.26×10-16).PLoS Computational Biology 03/2014; 10(3):e1003518. DOI:10.1371/journal.pcbi.1003518 · 4.83 Impact Factor