Complex variation in measures of general intelligence and cognitive change.
Complex variation in measures of general intelligence and cognitive change.
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一般智力和认知变化的衡量标准的复杂变化。
DOI：
10.1371/journal.pone.0081189
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Tenesa A
中科院分区：
文献类型：
--
作者：
Rowe SJ;Rowlatt A;Davies G;Harris SE;Porteous DJ;Liewald DC;McNeill G;Starr JM;Deary IJ;Tenesa A
结合来自多个SNP的信息可以捕获比来自单个SNP效应的总和更大量的遗传变异，并有助于识别缺失的遗传力。区域可以捕获来自多个小影响的常见变体、多个罕见变体或两者的组合的变化。我们描述了人类认知的区域遗传力映射。成年晚期（64-79岁）的结晶智力（gc）和液体智力（gf）的测量可用于1806个个体的549，692个常染色体单核苷酸多态性（SNP）基因分型。同样的人在11岁时接受了测试，这使我们有机会测量他们一生中大部分时间的认知变化。547,750个按位置排列的SNPs被分为10908个重叠区域，每个区域有101个SNPs，以估计每个区域解释的遗传变异，这种方法类似于经典的连锁方法。我们还估计了由个体常染色体和基因内SNP解释的遗传变异。经验显着性阈值估计分别为每个性状从全基因组扫描的500排列数据集。单个区域的似然比检验的5%显著性阈值范围为三个性状的17-17.5。这相当于在卡方分布（1df和0之间）P<1.44×10−5的预期下的名义显著性。这些阈值表明，这种类型的方差分量分析的似然比检验的分布应根据经验进行估计。此外，我们表明，这些地区解释的变化估计可以严重高估。应用置换阈值后，5号染色体上跨越PRRC 1基因的GF区域在全基因组10%的经验阈值下是显著的。颞叶皮层基因甲基化分析为PRRC 1与流体智力的关联提供了支持（P = 0.004），并为这些独特信息队列的高通量测序提供了主要候选基因。
Combining information from multiple SNPs may capture a greater amount of genetic variation than from the sum of individual SNP effects and help identifying missing heritability. Regions may capture variation from multiple common variants of small effect, multiple rare variants or a combination of both. We describe regional heritability mapping of human cognition. Measures of crystallised (gc) and fluid intelligence (gf) in late adulthood (64–79 years) were available for 1806 individuals genotyped for 549,692 autosomal single nucleotide polymorphisms (SNPs). The same individuals were tested at age 11, enabling us the rare opportunity to measure cognitive change across most of their lifespan. 547,750 SNPs ranked by position are divided into 10, 908 overlapping regions of 101 SNPs to estimate the genetic variance each region explains, an approach that resembles classical linkage methods. We also estimate the genetic variation explained by individual autosomes and by SNPs within genes. Empirical significance thresholds are estimated separately for each trait from whole genome scans of 500 permutated data sets. The 5% significance threshold for the likelihood ratio test of a single region ranged from 17–17.5 for the three traits. This is the equivalent to nominal significance under the expectation of a chi-squared distribution (between 1df and 0) of P<1.44×10−5. These thresholds indicate that the distribution of the likelihood ratio test from this type of variance component analysis should be estimated empirically. Furthermore, we show that estimates of variation explained by these regions can be grossly overestimated. After applying permutation thresholds, a region for gf on chromosome 5 spanning the PRRC1 gene is significant at a genome-wide 10% empirical threshold. Analysis of gene methylation on the temporal cortex provides support for the association of PRRC1 and fluid intelligence (P = 0.004), and provides a prime candidate gene for high throughput sequencing of these uniquely informative cohorts.
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影响因子：
4.1
作者：
Deary IJ;Gow AJ;Taylor MD;Corley J;Brett C;Wilson V;Campbell H;Whalley LJ;Visscher PM;Porteous DJ;Starr JM
通讯作者：
Starr JM
影响因子：
64.8
作者：
Deary, Ian J.;Yang, Jian;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
影响因子：
4.1
作者：
FERNANDO, RL;GROSSMAN, M
通讯作者：
GROSSMAN, M
影响因子：
4.9
作者：
HORN, JL;CATTELL, RB
通讯作者：
CATTELL, RB
影响因子：
5.8
作者：
Lee, S. H.;Yang, J.;Wray, N. R.
通讯作者：
Wray, N. R.