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The nature of nurture: a genomewide association scan for family chaos.

Butcher LM, Plomin R - Behav. Genet. (2008)

Bottom Line: We screened 490,041 autosomal single-nucleotide polymorphisms (SNPs) in a two-stage design in which children in low chaos families (N = 469) versus high chaos families (N = 369) from 3,000 families of 4-year-old twins were screened in Stage 1 using pooled DNA.Despite having 99% power to detect associations that account for more than 0.5% of the variance, none of the 41 nominated SNPs met conservative criteria for replication.Similar to GWA analyses of other complex traits, it is likely that most of the heritable variation in environmental measures such as family chaos is due to many genes of very small effect size.

View Article: PubMed Central - PubMed

Affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Box Number P082, De Crespigny Park, London, UK. l.butcher@ucl.ac.uk

ABSTRACT
Widely used measures of the environment, especially the family environment of children, show genetic influence in dozens of twin and adoption studies. This phenomenon is known as gene-environment correlation in which genetically driven influences of individuals affect their environments. We conducted the first genome-wide association (GWA) analysis of an environmental measure. We used a measure called CHAOS which assesses 'environmental confusion' in the home, a measure that is more strongly associated with cognitive development in childhood than any other environmental measure. CHAOS was assessed by parental report when the children were 3 years and again when the children were 4 years; a composite CHAOS measure was constructed across the 2 years. We screened 490,041 autosomal single-nucleotide polymorphisms (SNPs) in a two-stage design in which children in low chaos families (N = 469) versus high chaos families (N = 369) from 3,000 families of 4-year-old twins were screened in Stage 1 using pooled DNA. In Stage 2, following SNP quality control procedures, 41 nominated SNPs were tested for association with family chaos by individual genotyping an independent representative sample of 3,529. Despite having 99% power to detect associations that account for more than 0.5% of the variance, none of the 41 nominated SNPs met conservative criteria for replication. Similar to GWA analyses of other complex traits, it is likely that most of the heritable variation in environmental measures such as family chaos is due to many genes of very small effect size.

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Related in: MedlinePlus

A histogram illustrating the distribution of absolute allele frequency differences between low and high CHAOS groups derived through pooled DNA on microarrays. The y-axis indicates the number of SNPs and x-axis shows absolute allele frequency differences between low and high CHAOS groups. The figure shows that the vast majority of allele frequency differences are small and that the mean allele frequency between low and high CHAOS groups is about 0.027. The x-axis is elongated to accommodate outliers, which are a logical source of candidate SNPs to follow up. The total number of SNPs is 448,944 because SNPs represented by fewer than 6 out of 10 replicates were removed
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Fig1: A histogram illustrating the distribution of absolute allele frequency differences between low and high CHAOS groups derived through pooled DNA on microarrays. The y-axis indicates the number of SNPs and x-axis shows absolute allele frequency differences between low and high CHAOS groups. The figure shows that the vast majority of allele frequency differences are small and that the mean allele frequency between low and high CHAOS groups is about 0.027. The x-axis is elongated to accommodate outliers, which are a logical source of candidate SNPs to follow up. The total number of SNPs is 448,944 because SNPs represented by fewer than 6 out of 10 replicates were removed

Mentions: The average allele frequency for the low and high CHAOS groups was calculated for each SNP. The correlation between the low and high CHAOS groups was 0.992, indicating that the rank order of allele frequencies was highly reliable overall—a test analogous to genome control. Accordingly, between-group differences were small: Fig. 1 illustrates that 90% of the SNPs exhibited between-group differences smaller than 0.05, with a mean between-group absolute difference of 0.027 for the whole dataset (range: 0.00–0.28).Fig. 1


The nature of nurture: a genomewide association scan for family chaos.

Butcher LM, Plomin R - Behav. Genet. (2008)

A histogram illustrating the distribution of absolute allele frequency differences between low and high CHAOS groups derived through pooled DNA on microarrays. The y-axis indicates the number of SNPs and x-axis shows absolute allele frequency differences between low and high CHAOS groups. The figure shows that the vast majority of allele frequency differences are small and that the mean allele frequency between low and high CHAOS groups is about 0.027. The x-axis is elongated to accommodate outliers, which are a logical source of candidate SNPs to follow up. The total number of SNPs is 448,944 because SNPs represented by fewer than 6 out of 10 replicates were removed
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2480594&req=5

Fig1: A histogram illustrating the distribution of absolute allele frequency differences between low and high CHAOS groups derived through pooled DNA on microarrays. The y-axis indicates the number of SNPs and x-axis shows absolute allele frequency differences between low and high CHAOS groups. The figure shows that the vast majority of allele frequency differences are small and that the mean allele frequency between low and high CHAOS groups is about 0.027. The x-axis is elongated to accommodate outliers, which are a logical source of candidate SNPs to follow up. The total number of SNPs is 448,944 because SNPs represented by fewer than 6 out of 10 replicates were removed
Mentions: The average allele frequency for the low and high CHAOS groups was calculated for each SNP. The correlation between the low and high CHAOS groups was 0.992, indicating that the rank order of allele frequencies was highly reliable overall—a test analogous to genome control. Accordingly, between-group differences were small: Fig. 1 illustrates that 90% of the SNPs exhibited between-group differences smaller than 0.05, with a mean between-group absolute difference of 0.027 for the whole dataset (range: 0.00–0.28).Fig. 1

Bottom Line: We screened 490,041 autosomal single-nucleotide polymorphisms (SNPs) in a two-stage design in which children in low chaos families (N = 469) versus high chaos families (N = 369) from 3,000 families of 4-year-old twins were screened in Stage 1 using pooled DNA.Despite having 99% power to detect associations that account for more than 0.5% of the variance, none of the 41 nominated SNPs met conservative criteria for replication.Similar to GWA analyses of other complex traits, it is likely that most of the heritable variation in environmental measures such as family chaos is due to many genes of very small effect size.

View Article: PubMed Central - PubMed

Affiliation: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Box Number P082, De Crespigny Park, London, UK. l.butcher@ucl.ac.uk

ABSTRACT
Widely used measures of the environment, especially the family environment of children, show genetic influence in dozens of twin and adoption studies. This phenomenon is known as gene-environment correlation in which genetically driven influences of individuals affect their environments. We conducted the first genome-wide association (GWA) analysis of an environmental measure. We used a measure called CHAOS which assesses 'environmental confusion' in the home, a measure that is more strongly associated with cognitive development in childhood than any other environmental measure. CHAOS was assessed by parental report when the children were 3 years and again when the children were 4 years; a composite CHAOS measure was constructed across the 2 years. We screened 490,041 autosomal single-nucleotide polymorphisms (SNPs) in a two-stage design in which children in low chaos families (N = 469) versus high chaos families (N = 369) from 3,000 families of 4-year-old twins were screened in Stage 1 using pooled DNA. In Stage 2, following SNP quality control procedures, 41 nominated SNPs were tested for association with family chaos by individual genotyping an independent representative sample of 3,529. Despite having 99% power to detect associations that account for more than 0.5% of the variance, none of the 41 nominated SNPs met conservative criteria for replication. Similar to GWA analyses of other complex traits, it is likely that most of the heritable variation in environmental measures such as family chaos is due to many genes of very small effect size.

Show MeSH
Related in: MedlinePlus