| 1. |
- Bygren, Lars Olov, 1936-, et al.
(författare)
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Change in paternal grandmothers' early food supply influenced cardiovascular mortality of the female grandchildren
- 2014
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Ingår i: BMC Genetics. - : BioMed Central. - 1471-2156. ; 15, s. 12-
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study investigated whether large fluctuations in food availability during grandparents' early development influenced grandchildren's cardiovascular mortality. We reported earlier that changes in availability of food - from good to poor or from poor to good - during intrauterine development was followed by a double risk of sudden death as an adult, and that mortality rate can be associated with ancestors' childhood availability of food. We have now studied transgenerational responses (TGR) to sharp differences of harvest between two consecutive years' for ancestors of 317 people in Overkalix, Sweden. Results: The confidence intervals were very wide but we found a striking TGR. There was no response in cardiovascular mortality in the grandchild from sharp changes of early exposure, experienced by three of the four grandparents (maternal grandparents and paternal grandfathers). If, however, the paternal grandmother up to puberty lived through a sharp change in food supply from one year to next, her sons' daughters had an excess risk for cardiovascular mortality (HR 2.69, 95% confidence interval 1.05-6.92). Selection or learning and imitation are unlikely explanations. X-linked epigenetic inheritance via spermatozoa seemed to be plausible, with the transmission, limited to being through the father, possibly explained by the sex differences in meiosis. Conclusion: The shock of change in food availability seems to give specific transgenerational responses.
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| 2. |
- Bygren, Lars Olov, 1936-, et al.
(författare)
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Epigenetics or ephemeral genetics? : Reply to Senn
- 2006
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Ingår i: European Journal of Human Genetics. - : Nature publishing group. - 1018-4813 .- 1476-5438.
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Annan publikation (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Bygren, Lars Olov, 1936-, et al.
(författare)
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Longevity determined by parental ancestors' nutrition during their slow growth period
- 2001
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Ingår i: Acta Biotheoretica. - : Springer. - 0001-5342 .- 1572-8358. ; 49:1, s. 53-59
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Tidskriftsartikel (refereegranskat)abstract
- Social circumstances often impinge on later generations in a socio-economic manner, giving children an uneven start in life. Overfeeding and overeating might not be an exception. The pathways might be complex but one direct mechanism could be genomic imprinting and loss of imprinting. An intergenerational "feedforward" control loop has been proposed, that links grandparental nutrition with the grandchild's growth. The mechanism has been speculated to be a specific response, e.g. to their nutritional state, directly modifying the setting of the gametic imprint on one or more genes. This study raises the question: Can overnutrition during a child's slow growth period trigger such direct mechanisms and partly determine mortality? Data were collected by following-up a cohort born in 1905 in Överkalix parish, northernmost Sweden. The probands were characterised by their parents' or grandparents' access to food during their own slow growth period. Availability of food in the area was defined by referring to historical data on harvests and food prices, records of local community meetings and general historical facts.If there was a surfeit of food in the environment when the paternal grandfather was a 9–12 year old boy a shortening of the proband survival could be demonstrated. The influence of parents', maternal grandparents' and paternal grandmothers' access to food during their slow growth period was discounted in a multivariable analysis. The results are indicative of very early programming mechanisms in human adaptation to the social environment.
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| 4. |
- Håglin, Lena, et al.
(författare)
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All-cause mortality of patients with dyslipidemia up to 19 years after a multidisciplinary lifestyle modification programme : a randomized trial
- 2011
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - 1741-8267 .- 1741-8275. ; 18:1, s. 79-85
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many studies have shown that individual lifestyle factors are associated with cardiovascular mortality and all-cause mortality. Observational studies of comprehensive programmes have reported risk reductions. The objectives were to assess the long-term all-cause mortality by diagnosis in patients referred to a lifestyle modification programme, aimed at combating coronary heart disease and stroke. METHODS: A randomized trial with 325 patients referred to the centre between 1988 and 1989 for dyslipidemia, hypertension, type 2 diabetes and coronary heart disease; 239 patients were randomized to the programme, 86 randomized to usual care. Cases were admitted to the centre in groups of 30 for a 4-week residential comprehensive activity, in total 114 full-time hours, focusing on food preferences and selections, and physical exercise. The activities were repeated during a 4-day revisit to the centre 1 year and 5 years after the 4-week intervention. Controls were referred back to their doctors, mainly in primary care, for usual care. Main outcome measure was all-cause mortality during 11-12 and 18-19 years after intervention. RESULTS: At follow-up 11-12 years after referral, the relative risk reduction (RRR) was 76% with the intention-to-treat analysis among cases admitted for dyslipidemia (hazards ratio 0.24, confidence interval 0.06-0.89, P=0.033). After 18-19 years, the RRR was 66% (hazards ratio 0.34, confidence interval 0.13-0.88, P=0.026). No RRR was found for the other three diagnoses. CONCLUSION: Patients admitted for dyslipidemia reached a real long-term RRR of all-cause mortality. They had by definition a need for this programme.
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| 5. |
- Kaati, Gunnar
(författare)
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Ancestral influences on health of grandchildren
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The late effects in adulthood of nutrition during adolescence, childhood, infancy, and the fetal and embryonic stages of development have attracted much attention in research, but less so the time of development of the genome. The issue of fetal origins of adult disease has particularly attracted interest. The effects are caused by nutritional constraints at critical phases of key fetal organ development. The general question pursued here is whether there are transgenerational effects. It is suggested that nutrients transiently influence the expression of specific subsets of genes during the slow growth period just before the prepubertal peak in growth velocity of children. Food availability during the slow growth period (SGP) just before the prepubertal peak in growth velocity of the paternal grandfather exerted an effect on longevity of their grandchildren (Paper I). Scarcity of food in the paternal grandfather's SGP was associated with extended survival of his grandchildren, whilst food abundance was associated with shortened life span of the grandchildren. One explanation was genomic imprinting, an intergenerational "feedforward" control loop linking grandparental nutrition with the grandchild's growth. Cardiovascular and diabetes related deaths were the outcomes. It was showed that cardiovascular mortality was reduced with poor availability of food in the father's SW, but also with good availability in the mother's SGP (Paper II). If the paternal grandfather was exposed to a surfeit of food during his SW, the proband had a fourfold excess mortality related to diabetes (OR 4.1, 95% c.i. 1.33-12.9 p=0.01) when age at death and the effects of parents and other grandparents exposure to food availability during their SGP were taken into account. A father's exposure to a surfeit of food during his SW, on the other hand, tended to protect the proband from diabetes. The effects were sex-specific; the paternal grandfather's food supply during the SGP was only linked to the mortality of grandsons, whilst paternal grandmother's food supply was only associated with the granddaughter's mortality (Paper Ill). Onset of paternal smoking during the SGP was associated with shorter mean gestational length of sons, but not of daughters. This indicates the existence of an inheritance with the sex-specific patterns of transmission suggesting a direct role for the Y chromosome and possible the X chromosome. Finally, the transgenerational sex-specific paternal grandpaternal/ grandchild effects and the effects of the proband's own early life circumstances were analysed (Paper IV). The transgenerational influence remained and the social circumstances were found important for the longevity of probands. In conclusion, the study explored the possible transgenerational effects from exposures occurring during the SGP prior to the prepubertal peak growth velocity. Such exposures seemed to influence gene expression in the next generation(s).
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| 6. |
- Kaati, Gunnar, 1940-, et al.
(författare)
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Cardiovascular and diabetes mortality determined by nutrition during parents' and grandparents' slow growth period
- 2002
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 10:11, s. 682-688
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Tidskriftsartikel (refereegranskat)abstract
- Overfeeding and overeating in families are traditions that are often transferred from generation to generation. Irrespective of these family traditions, food availability might lead to overfeeding, in its turn leading to metabolic adaptations. Apart from selection, could these adaptations to the social environment have transgenerational effects? This study will attempt to answer the following question: Can overeating during a child's slow growth period (SGP), before their prepubertal peak in growth velocity influence descendants' risk of death from cardiovascular disease and diabetes? Data were collected by following three cohorts born in 1890, 1905 and 1920 in Överkalix parish in northern Sweden up until death or 1995. The parents' or grandparents' access to food during their SGP was determined by referring to historical data on harvests and food prices, records of local community meetings and general historical facts. If food was not readily available during the father's slow growth period, then cardiovascular disease mortality of the proband was low. Diabetes mortality increased if the paternal grandfather was exposed to a surfeit of food during his slow growth period. (Odds Ratio 4.1, 95% confidence interval 1.33-12.93, P=0.01). Selection bias seemed to be unlikely. A nutrition-linked mechanism through the male line seems to have influenced the risk for cardiovascular and diabetes mellitus mortality.
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| 7. |
- Kaati, Gunnar
(författare)
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Case studies on epigenetic inheritance
- 2009
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Ingår i: Epigenetics and human health. - Weinheim, Germany : Wiley-VCH Verlagsgesellschaft. - 9783527324279 - 9783527628384 ; , s. 63-86
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Bokkapitel (refereegranskat)abstract
- The effects in adulthood of nutrition during adolescence, childhood, infancy, and the fetal and embryonic stages of development have attracted much attention in research. It is argued that the effects (adult diseases) are caused by nutritional constraints at critical phases of key fetal organ development. Here it is asked whether there are transgenerational effects. It is suggested that various nutrients transiently influence the expression of specific subsets of genes during the slow growth period just before the prepubertal peak in growth velocity of children. Food availability during the slow growth period (SGP) just before the prepubertal peak in growth velocity of the paternal grandfather exerted an effect on the longevity of his grandchildren. Scarcity of food in the paternal grandfather's SGP was associated with significant extended survival of his grandchildren, while food abundance was associated with shortened life span of the grandchildren. One explanation was genomic imprinting, an intergenerational "feedforward" control loop linking grandparental nutrition with the grandchild's growth. Cardiovascular mortality was reduced with poor availability of food in the father's SGP, but also with good availability in the mother's SGP. If the paternal grandfather was exposed to a surfeit of food during his SGP, the proband had a fourfold excess mortality related to diabetes. A father's exposure to a surfeit of food during his SGP, on the other hand, tended to protect the proband from diabetes. The effects were sex-specific; the paternal grandfather's food supply was only linked to the mortality of grandsons, while the paternal grandmother's food supply was only associated with the granddaughter's mortality. This indicates the existence of a direct biological transgenerational effect, an epigenetic inheritance with the sex-specific patterns of transmission suggesting a direct role for the Y chromosome and possible the X chromosome. The effects were not the result of the proband's own early life during childhood, and/or effects of genetic selection. In conclusion, the studies explored the possible transgenerational effects from exposures occurring during the SGP prior to the prepubertal peak growth velocity. Such exposures seemed to influence gene expression in the next generation(s).
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| 8. |
- Kaati, Gunnar, et al.
(författare)
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Outcomes of comprehensive lifestyle modification in inpatient setting
- 2006
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Ingår i: Patient Education and Counseling. - Clare : Elsevier. - 0738-3991 .- 1873-5134. ; 62:1, s. 95-103
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the effectiveness of a 4-week inpatient non-pharmacological risk factor modification programme for individuals with the metabolic syndrome. The aim of the program was to reduce patients' over risks for stroke and myocardial infarction.Methods: A prospective clinical study including 2468 patients - 1096 men and 1372 women - with and average age of 50 +/- 10 years. The patients were referred to the programme from primary care units and hospitals where treatment options were exhausted.Results: All risk factor levels for stroke and myocardial infarction decreased. The reduction of weight among men was 4.7 +/- 2.6 kg and 3.8 +/- 1.8 kg among women from an initial weight of 96 17 kg and 85 +/- 16 kg. respectively. The patients systolic and diastolic blood pressure decreased by 15/10 mm Hg for men and 14/9 min Hg among women from initial average for the whole population of 148/90 +/- 19/11 mm Hg and 146/87 +/- 19/12 min Hg, respectively. The greatest decrease in weight and blood pressure occurred in men and women with an initial body mass index of >= 30 and with a diastolic blood pressure of >= 90; in this group, the average reductions in weight were 5.8 +/- 2.4 kg for men and 4.4 +/- 1.7 kg for women; the reductions in systolisk/diastolisk blood pressure were 22/15 +/- 16/9 mm Hg (p < 0.001) for both men and women. A reduction of medication (DDD) although not a goal was also achieved.Conclusion: The results prove the value of a comprehensive and highly structured inpatient approach to lifestyle modification. Practice implications: The results should give cause to trials with half-way strategies integrating features from the inpatient programme into the design of risk factor interventions.
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| 9. |
- Kaati, Gunnar, et al.
(författare)
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Transgenerational response to nutrition, early life circumstances and longevity
- 2007
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Ingår i: European Journal of Human Genetics. - London : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 15:7, s. 784-790
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Tidskriftsartikel (refereegranskat)abstract
- Nutrition might induce, at some loci, epigenetic or other changes that could be transmitted to the next generation impacting on health. The slow growth period (SGP) before the prepubertal peak in growth velocity has emerged as a sensitive period where different food availability is followed by different transgenerational response (TGR). The aim of this study is to investigate to what extent the probands own childhood circumstances are in fact the determinants of the findings. In the analysis, data from three random samples, comprising 271 probands and their 1626 parents and grandparents, left after exclusions because of missing data, were utilized. The availability of food during any given year was classified based on regional statistics. The ancestors' SGP was set at the ages of 8-12 years and the availability of food during these years classified as good, intermediate or poor. The probands' childhood circumstances were defined by the father's ownership of land, the number of siblings and order in the sibship, the death of parents and the parents' level of literacy. An earlier finding of a sex-specific influence from the ancestors' nutrition during the SGP, going from the paternal grandmother to the female proband and from the paternal grandfather to the male proband, was confirmed. In addition, a response from father to son emerged when childhood social circumstances of the son were accounted for. Early social circumstances influenced longevity for the male proband. TGRs to ancestors' nutrition prevailed as the main influence on longevity.
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| 10. |
- Pembrey, Marcus E., et al.
(författare)
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Sex-specific, male-line transgenerational responses in humans
- 2006
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Ingår i: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 14, s. 159-166
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Tidskriftsartikel (refereegranskat)abstract
- Transgenerational effects of maternal nutrition or other environmental 'exposures' are well recognised, but the possibility of exposure in the male influencing development and health in the next generation(s) is rarely considered. However, historical associations of longevity with paternal ancestors' food supply in the slow growth period (SGP) in mid childhood have been reported. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we identified 166 fathers who reported starting smoking before age 11 years and compared the growth of their offspring with those with a later paternal onset of smoking, after correcting for confounders. We analysed food supply effects on offspring and grandchild mortality risk ratios (RR) using 303 probands and their 1818 parents and grandparents from the 1890, 1905 and 1920 Överkalix cohorts, northern Sweden. After appropriate adjustment, early paternal smoking is associated with greater body mass index (BMI) at 9 years in sons, but not daughters. Sex-specific effects were also shown in the Överkalix data; paternal grandfather's food supply was only linked to the mortality RR of grandsons, while paternal grandmother's food supply was only associated with the granddaughters' mortality RR. These transgenerational effects were observed with exposure during the SGP (both grandparents) or fetal/infant life (grandmothers) but not during either grandparent's puberty. We conclude that sex-specific, male-line transgenerational responses exist in humans and hypothesise that these transmissions are mediated by the sex chromosomes, X and Y. Such responses add an entirely new dimension to the study of gene–environment interactions in development and health.
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