Assessing individual differences in genome-wide gene expression in human whole blood: reliability over four hours and stability over 10 months.
Studying the causes and correlates of natural variation in gene expression in healthy populations assumes that individual differences in gene expression can be reliably and stably assessed across time. However, this is yet to be established. We examined 4-hour test-retest reliability and 10 month test-retest stability of individual differences in gene expression in ten 12-year-old children. Blood was collected on four occasions: 10 a.m. and 2 p.m. on Day 1 and 10 months later at 10 a.m. and 2 p.m. Total RNA was hybridized to Affymetrix-U133 plus 2.0 arrays. For each probeset, the correlation across individuals between 10 a.m. and 2 p.m. on Day 1 estimates test-retest reliability. We identified 3,414 variable and abundantly expressed probesets whose 4-hour test-retest reliability exceeded .70, a conventionally accepted level of reliability, which we had 80% power to detect. Of the 3,414 reliable probesets, 1,752 were also significantly reliable 10 months later. We assessed the long-term stability of individual differences in gene expression by correlating the average expression level for each probe-set across the two 4-hour assessments on Day 1 with the average level of each probe-set across the two 4-hour assessments 10 months later. 1,291 (73.7%) of the 1,752 probe-sets that reliably detected individual differences across 4 hours on two occasions, 10 months apart, also stably detected individual differences across 10 months. Heritability, as estimated from the MZ twin intraclass correlations, is twice as high for the 1,752 reliable probesets versus all present probesets on the array (0.68 vs 0.34), and is even higher (0.76) for the 1,291 reliable probesets that are also stable across 10 months. The 1,291 probesets that reliably detect individual differences from a single peripheral blood collection and stably detect individual differences over 10 months are promising targets for research on the causes (e.g., eQTLs) and correlates (e.g., psychopathology) of individual differences in gene expression.
Meaburn
Emma L
EL
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom. e.meaburn@iop.kcl.ac.uk
Fernandes
Cathy
C
Craig
Ian W
IW
Plomin
Robert
R
Schalkwyk
Leonard C
LC
D002648:Child; D030541:Databases, Genetic; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000097:blood / Q000235:genetics; D015203:Reproducibility of Results; D014430:Twins, Monozygotic / Q000235:genetics
D012313:RNA