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Genome-scan for IQ discrepancy in autism: evidence for loci on chromosomes 10 and 16.

ABSTRACT: Performance IQ (PIQ) greater than verbal IQ (VIQ) is often observed in studies of the cognitive abilities of autistic individuals. This characteristic is correlated with social and communication impairments, key parts of the autism diagnosis. We present the first genetic analyses of IQ discrepancy (PIQ-VIQ) as an autism-related phenotype. We performed genome-wide joint linkage and segregation analyses on 287 multiplex families, using a Markov chain Monte Carlo approach. Genetic data included a genome-scan of 387 micro-satellite markers in 210 families augmented with additional markers added in a subset of families. Empirical P values were calculated for five interesting regions. Linkage analysis identified five chromosomal regions with substantial regional evidence of linkage; 10p12 [P = 0.001; genome-wide (gw) P = 0.05], 16q23 (P = .015; gw P = 0.53), 2p21 (P = 0.03, gw P = 0.78), 6q25 (P = 0.047, gw P = 0.91) and 15q23-25 (P = 0.053, gw P = 0.93). The location of the chromosome 10 linkage signal coincides with a region noted in a much earlier genome-scan for autism, and the chromosome 16 signal coincides exactly with a linkage signal for non-word repetition in specific language impairment. This study provides strong evidence for a QTL influencing IQ discrepancy in families with autistic individuals on chromosome 10, and suggestive evidence for a QTL on chromosome 16. The location of the chromosome 16 signal suggests a candidate gene, CDH13, a T-cadherin expressed in the brain, which has been implicated in previous SNP studies of autism and ADHD.

SUBMITTER: Chapman NH

PROVIDER: S-EPMC3082447 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Genome-scan for IQ discrepancy in autism: evidence for loci on chromosomes 10 and 16.

Chapman Nicola H NH Estes Annette A Munson Jeff J Bernier Raphael R Webb Sara J SJ Rothstein Joseph H JH Minshew Nancy J NJ Dawson Geraldine G Schellenberg Gerard D GD Wijsman Ellen M EM

Human genetics 20101021 1

Performance IQ (PIQ) greater than verbal IQ (VIQ) is often observed in studies of the cognitive abilities of autistic individuals. This characteristic is correlated with social and communication impairments, key parts of the autism diagnosis. We present the first genetic analyses of IQ discrepancy (PIQ-VIQ) as an autism-related phenotype. We performed genome-wide joint linkage and segregation analyses on 287 multiplex families, using a Markov chain Monte Carlo approach. Genetic data included a g ...[more]

PMID: 20963441

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Project description:Obesity is a multigenic trait that has a substantial genetic component. Animal models confirm a role for gene-gene interactions, and human studies suggest that as much as one-third of the heritable variance may be due to nonadditive gene effects. To evaluate potential epistatic interactions among five regions, on chromosomes 7, 10, and 20, that have previously been linked to obesity phenotypes, we conducted pairwise correlation analyses based on alleles shared identical by descent (IBD) for independent obese affected sibling pairs (ASPs), and we determined family-specific nonparametric linkage (NPL) scores in 244 families. The correlation analyses were also conducted separately, by race, through use of race-specific allele frequencies. Conditional analyses for a qualitative trait (body mass index [BMI] >/=27) and hierarchical models for quantitative traits were used to further refine evidence of gene interaction. Both the ASP-specific IBD-sharing probability and the family-specific NPL score revealed that there were strong positive correlations between 10q (88-97 cM) and 20q (65-83 cM), through single-point and multipoint analyses with three obesity thresholds (BMI >/=27, >/=30, and >/=35) across African American and European American samples. Conditional analyses for BMI >/=27 found that the LOD score at 20q rises from 1.53 in the baseline analysis to 2.80 (empirical P=.012) when families were weighted by evidence for linkage at 10q (D10S1646) through use of zero-one weights (weight(0-1)) and to 3.32 (empirical P<.001) when proportional weights (weight(prop)) were used. For percentage fat mass, variance-component analysis based on a two-locus epistatic model yielded significant evidence for interaction between 20q (75 cM) and the chromosome 10 centromere (LOD = 1.74; P=.024), compared with a two-locus additive model (LOD = 0.90). The results from multiple methods and correlated phenotypes are consistent in suggesting that epistatic interactions between loci in these regions play a role in extreme human obesity.

Dataset Information

Genome-scan for IQ discrepancy in autism: evidence for loci on chromosomes 10 and 16.

Publications

Genome-scan for IQ discrepancy in autism: evidence for loci on chromosomes 10 and 16.

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