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6148名撒丁岛人的心血管和人格特质的遗传力

Heritability of cardiovascular and personality traits in 6,148 Sardinians.

作者信息

Pilia Giuseppe, Chen Wei-Min, Scuteri Angelo, Orrú Marco, Albai Giuseppe, Dei Mariano, Lai Sandra, Usala Gianluca, Lai Monica, Loi Paola, Mameli Cinzia, Vacca Loredana, Deiana Manila, Olla Nazario, Masala Marco, Cao Antonio, Najjar Samer S, Terracciano Antonio, Nedorezov Timur, Sharov Alexei, Zonderman Alan B, Abecasis Gonçalo R, Costa Paul, Lakatta Edward, Schlessinger David

机构信息

Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Ospedale Microcitemico, Cagliari, Italy.

出版信息

PLoS Genet. 2006 Aug 25;2(8):e132. doi: 10.1371/journal.pgen.0020132. Epub 2006 Jul 10.

Abstract

In family studies, phenotypic similarities between relatives yield information on the overall contribution of genes to trait variation. Large samples are important for these family studies, especially when comparing heritability between subgroups such as young and old, or males and females. We recruited a cohort of 6,148 participants, aged 14-102 y, from four clustered towns in Sardinia. The cohort includes 34,469 relative pairs. To extract genetic information, we implemented software for variance components heritability analysis, designed to handle large pedigrees, analyze multiple traits simultaneously, and model heterogeneity. Here, we report heritability analyses for 98 quantitative traits, focusing on facets of personality and cardiovascular function. We also summarize results of bivariate analyses for all pairs of traits and of heterogeneity analyses for each trait. We found a significant genetic component for every trait. On average, genetic effects explained 40% of the variance for 38 blood tests, 51% for five anthropometric measures, 25% for 20 measures of cardiovascular function, and 19% for 35 personality traits. Four traits showed significant evidence for an X-linked component. Bivariate analyses suggested overlapping genetic determinants for many traits, including multiple personality facets and several traits related to the metabolic syndrome; but we found no evidence for shared genetic determinants that might underlie the reported association of some personality traits and cardiovascular risk factors. Models allowing for heterogeneity suggested that, in this cohort, the genetic variance was typically larger in females and in younger individuals, but interesting exceptions were observed. For example, narrow heritability of blood pressure was approximately 26% in individuals more than 42 y old, but only approximately 8% in younger individuals. Despite the heterogeneity in effect sizes, the same loci appear to contribute to variance in young and old, and in males and females. In summary, we find significant evidence for heritability of many medically important traits, including cardiovascular function and personality. Evidence for heterogeneity by age and sex suggests that models allowing for these differences will be important in mapping quantitative traits.

摘要

在家族研究中,亲属之间的表型相似性可提供有关基因对性状变异总体贡献的信息。对于这些家族研究而言,大样本很重要,尤其是在比较不同亚组(如年轻人和老年人、男性和女性)之间的遗传力时。我们从撒丁岛的四个聚居城镇招募了一个由6148名年龄在14至102岁之间的参与者组成的队列。该队列包括34469对亲属。为了提取遗传信息,我们实施了用于方差成分遗传力分析的软件,该软件旨在处理大型家系、同时分析多个性状并对异质性进行建模。在此,我们报告了对98个数量性状的遗传力分析,重点关注人格和心血管功能方面。我们还总结了所有性状对的双变量分析结果以及每个性状的异质性分析结果。我们发现每个性状都有显著的遗传成分。平均而言,遗传效应解释了38项血液检测中40%的变异、5项人体测量指标中51%的变异、20项心血管功能指标中25%的变异以及35项人格特质中19%的变异。四项性状显示出存在X连锁成分的显著证据。双变量分析表明,许多性状存在重叠的遗传决定因素,包括多种人格方面以及与代谢综合征相关的几种性状;但我们没有发现可能是某些人格性状与心血管危险因素之间已报道关联基础的共享遗传决定因素的证据。考虑异质性的模型表明,在这个队列中,遗传方差通常在女性和较年轻个体中更大,但也观察到了有趣的例外情况。例如,42岁以上个体的血压狭义遗传力约为26%,而较年轻个体中仅约为8%。尽管效应大小存在异质性,但相同的基因座似乎在年轻人和老年人以及男性和女性中都对变异有贡献。总之,我们发现许多医学上重要的性状(包括心血管功能和人格)具有遗传力的显著证据。年龄和性别导致的异质性证据表明,考虑这些差异的模型对于绘制数量性状图谱将很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/34fc/1557782/fa2a48cf7190/pgen.0020132.g001.jpg

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