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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 scatterplot showing the 48 top-ranked SNPs (crosses) against the background of 448,994 unselected SNPs comparing allele frequencies for the low CHAOS group (x-axis) and the high CHAOS group (y-axis). The figure also displays the density of SNPs as a function of low CHAOS versus high CHAOS allele frequency differences; density of SNP clusters increases as the heat map changes from light grey (sparse clusters) though to dark grey (dense clusters). Allele frequency differences are small with the majority of small differences occurring for SNPs with minor allele frequencies of 0.10–0.25, which reflects the representation of SNPs with these allele frequencies on the Affymetrix microarray. The correlation between low and high CHAOS allele frequencies was 0.992 indicating high reliability of the rank order of allele frequencies across the low and high CHAOS groups
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Fig2: A scatterplot showing the 48 top-ranked SNPs (crosses) against the background of 448,994 unselected SNPs comparing allele frequencies for the low CHAOS group (x-axis) and the high CHAOS group (y-axis). The figure also displays the density of SNPs as a function of low CHAOS versus high CHAOS allele frequency differences; density of SNP clusters increases as the heat map changes from light grey (sparse clusters) though to dark grey (dense clusters). Allele frequency differences are small with the majority of small differences occurring for SNPs with minor allele frequencies of 0.10–0.25, which reflects the representation of SNPs with these allele frequencies on the Affymetrix microarray. The correlation between low and high CHAOS allele frequencies was 0.992 indicating high reliability of the rank order of allele frequencies across the low and high CHAOS groups

Mentions: As explained in Methods, SNPs selected for individual genotyping in Stage 2 were chosen on the basis of a ranked composite score which took into account the between-group allele frequency difference, variance between- and within-biological replicate microarrays, number of successfully assayed arrays and minor allele frequency. Due to financial restrictions, we were limited to individually genotyping in SNPlex a single probeset of 48 SNPs with the highest composite scores. The mean absolute difference between low and high SNP-MaP allele frequency estimates for these 48 SNPs was 0.11 (ranging from 0.05 to 0.24). The seven SNPs with the largest between-group allele frequency differences were not selected as they exhibited high levels of variance, which counted unfavorably in the composite selection score. Figure 2 places the 48 selected SNPs in the context of the full dataset by plotting the average allele frequency of the low CHAOS group against that of the high CHAOS group. Details about the 48 selected SNPs can be found in Table 1.Fig. 2


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

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

A scatterplot showing the 48 top-ranked SNPs (crosses) against the background of 448,994 unselected SNPs comparing allele frequencies for the low CHAOS group (x-axis) and the high CHAOS group (y-axis). The figure also displays the density of SNPs as a function of low CHAOS versus high CHAOS allele frequency differences; density of SNP clusters increases as the heat map changes from light grey (sparse clusters) though to dark grey (dense clusters). Allele frequency differences are small with the majority of small differences occurring for SNPs with minor allele frequencies of 0.10–0.25, which reflects the representation of SNPs with these allele frequencies on the Affymetrix microarray. The correlation between low and high CHAOS allele frequencies was 0.992 indicating high reliability of the rank order of allele frequencies across the low and high CHAOS groups
© Copyright Policy
Related In: Results  -  Collection

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

Fig2: A scatterplot showing the 48 top-ranked SNPs (crosses) against the background of 448,994 unselected SNPs comparing allele frequencies for the low CHAOS group (x-axis) and the high CHAOS group (y-axis). The figure also displays the density of SNPs as a function of low CHAOS versus high CHAOS allele frequency differences; density of SNP clusters increases as the heat map changes from light grey (sparse clusters) though to dark grey (dense clusters). Allele frequency differences are small with the majority of small differences occurring for SNPs with minor allele frequencies of 0.10–0.25, which reflects the representation of SNPs with these allele frequencies on the Affymetrix microarray. The correlation between low and high CHAOS allele frequencies was 0.992 indicating high reliability of the rank order of allele frequencies across the low and high CHAOS groups
Mentions: As explained in Methods, SNPs selected for individual genotyping in Stage 2 were chosen on the basis of a ranked composite score which took into account the between-group allele frequency difference, variance between- and within-biological replicate microarrays, number of successfully assayed arrays and minor allele frequency. Due to financial restrictions, we were limited to individually genotyping in SNPlex a single probeset of 48 SNPs with the highest composite scores. The mean absolute difference between low and high SNP-MaP allele frequency estimates for these 48 SNPs was 0.11 (ranging from 0.05 to 0.24). The seven SNPs with the largest between-group allele frequency differences were not selected as they exhibited high levels of variance, which counted unfavorably in the composite selection score. Figure 2 places the 48 selected SNPs in the context of the full dataset by plotting the average allele frequency of the low CHAOS group against that of the high CHAOS group. Details about the 48 selected SNPs can be found in Table 1.Fig. 2

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