Time to take epigenetic inheritance seriously
Time to take epigenetic inheritance seriously
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是时候认真对待表观遗传了
DOI：
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发表时间：
2002
影响因子：
5.2
通讯作者：
M. Pembrey
中科院分区：
文献类型：
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作者：
M. Pembrey
任何对跨代影响的研究都需要跨越几代人的信息，而这在人类身上是不容易获得的。关于祖父母的暴露对孙辈后代结局的影响的研究很少，但本期第682-688页报道的一项这样的研究迫使我们直面表观遗传顺着男性遗传的可能性。这就是瑞典Umea大学的Kaati、Bygren和Edvinsson的工作对人类遗传学家的重要性。基于他们对早期营养对心血管死亡率影响的兴趣，他们利用了瑞典北部一个与世隔绝的社区的年度收获记录，这些记录可以追溯到1799年，以探索食物供应对三代人的影响。该团队早先对一个出生于1905年的队列进行的研究表明，在祖父青春期前的缓慢生长期(SGP)，食物的可获得性对先证者的寿命有显著影响。在祖父的SGP中，食物稀缺与孙子孙女的寿命显著延长有关，而食物丰富与孙子孙女的寿命大大缩短有关。只有四种可能的解释：营养诱导的表观遗传修饰的染色体传递，通过差异生存/生育进行的激烈基因选择，统计学上的怪癖或产生错误关联的隐藏偏见，或者一些尚未发现的遗传机制。在目前的研究中，Kaati和他的同事扩大了样本，增加了两个出生于1890年和1920年的新队列，以便有能力专门研究与心血管和糖尿病相关的死亡。之所以选择后一种结果，是因为印记基因与糖尿病风险有关。首先要说的是，当父亲的祖父在SGP期间接触到大量食物时，先证者的存活时间较短，这一现象在新研究的1890年队列中得到了复制，尽管这种联系在1920年的队列中无法得到证明。总体而言，他们表明，父亲的SGP中食物的可获得性较差，但母亲的SGP中食物的可获得性较好，从而降低了心血管死亡率。父母营养的这种相互作用本身就很有趣，但最引人注目的结果是糖尿病。如果父亲的祖父在他的SGP期间暴露于过量的食物中，那么先证者与糖尿病相关的超额死亡率是四倍(OR 4.1，95%C.I.1.33-12.93，P=0.01)，考虑到死亡年龄和父母和祖父母在各自的SGP期间可能过度饮食的影响。有趣的是，父亲在SGP期间暴露在过量食物中往往会保护先证者免受糖尿病的影响(OR 0.13，95%C.I.0.02-1.07，P=0.06)，暗示了世代之间的拉锯战效应。结果越出人意料，在其他队列中复制研究结果就越重要。在瑞典北部，这应该是可能的，这在一定程度上要归功于国王陛下过去要求的地区收成记录。
Rich pickings from the past Any study of transgenerational effects needs information from across the generations, and this is not easy to obtain in humans. There is little research on the effect of exposures in grandparents on outcomes in their grandchildren, but one such study, reported on pages 682 – 688 of this issue, obliges us to confront the possibility of epigenetic inheritance down the male line. Herein lies the importance for human geneticists of the work of Kaati, Bygren and Edvinsson from Umea University, Sweden. Building on their interest in early nutritional influences on cardiovascular mortality, they have exploited records of annual harvests from an isolated community in northern Sweden that go back as far as 1799 to explore the effects of food availability across three generations. Earlier work by the team on a cohort born in 1905 showed a remarkable effect of food availability during the slow growth period (SGP) just before puberty of the paternal grandfather on the longevity of the probands. Scarcity of food in grandfather’s SGP was associated with a significantly extended survival of his grandchildren for many years, whilst food abundance was associated with a greatly shortened life span of the grandchildren. There are only four possible explanations; chromosomal transmission of nutritionally-induced epigenetic modifications, intense genetic selection through differential survival /fertility, a statistical quirk or hidden bias producing a false association, or some mechanism of inheritance yet to be discovered. In the present study Kaati and colleagues have enlarged the sample with two new cohorts born in 1890 and 1920 in order to have the power to look specifically at cardiovascular and diabetes related deaths. The latter outcome was chosen because imprinted genes have been implicated in diabetes risk. The first thing to say is that the shorter survival of probands when the paternal grandfather had been exposed to plenty of food during his SGP was replicated in the newly studied 1890 cohort, although this association could not be demonstrated in the 1920 cohort. Overall they show that cardiovascular mortality was reduced with poor availability of food in the father’s SGP, but also with good availability in the mother’s SGP. This reciprocal effect of parental nutrition is intriguing in itself, but the most striking result comes with diabetes. If the paternal grandfather was exposed to a surfeit of food during his SGP, then the proband had a fourfold excess mortality related to diabetes (OR 4.1, 95% c.i.1.33 – 12.93, P=0.01) when age at death and the effects of possible over eating among parents and grandparents during their respective SGP were taken into account. Interestingly a father’s exposure to a surfeit of food during his SGP tended to protect the proband from diabetes (OR 0.13, 95% c.i. 0.02 – 1.07, P=0.06), hinting at some ‘see-saw’ effect down the generations. The more unexpected the result, the more important it is to replicate the findings on other cohorts. This should be possible in northern Sweden thanks, in part, to the regional harvest records that were demanded by His Majesty the King in times gone by.