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Article ; Online: A new blood based epigenetic age predictor for adolescents and young adults

Håvard Aanes / Øyvind Bleka / Pål Skage Dahlberg / Kristina Totland Carm / Terho Lehtimäki / Olli Raitakari / Mika Kähönen / Mikko Hurme / Veslemøy Rolseth

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 10

Abstract: Abstract Children have special rights for protection compared to adults in our society. However, more than 1/4 of children globally have no documentation of their date of birth. Hence, there is a pressing need to develop biological methods for ... ...

Abstract	Abstract Children have special rights for protection compared to adults in our society. However, more than 1/4 of children globally have no documentation of their date of birth. Hence, there is a pressing need to develop biological methods for chronological age prediction, robust to differences in genetics, psychosocial events and physical living conditions. At present, DNA methylation is the most promising biological biomarker applied for age assessment. The human genome contains around 28 million DNA methylation sites, many of which change with age. Several epigenetic clocks accurately predict chronological age using methylation levels at age associated GpG-sites. However, variation in DNA methylation increases with age, and there is no epigenetic clock specifically designed for adolescents and young adults. Here we present a novel age Predictor for Adolescents and Young Adults (PAYA), using 267 CpG methylation sites to assess the chronological age of adolescents and young adults. We compared different preprocessing approaches and investigated the effect on prediction performance of the epigenetic clock. We evaluated performance using an independent validation data set consisting of 18-year-old individuals, where we obtained a median absolute deviation of just below 0.7 years. This tool may be helpful in age assessment of adolescents and young adults. However, there is a need to investigate the robustness of the age predictor across geographical and disease populations as well as environmental effects.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The relationship of socioeconomic status in childhood and adulthood with compassion

Aino I Saarinen / Dacher Keltner / Henrik Dobewall / Terho Lehtimäki / Liisa Keltikangas-Järvinen / Mirka Hintsanen

PLoS ONE, Vol 16, Iss 3, p e

A study with a prospective 32-year follow-up.

2021 Volume 0248226

Abstract: The objective of this study was to investigate (i) whether childhood family SES predicts offspring's compassion between ages 20-50 years and (ii) whether adulthood SES predicts compassion or vice versa. We used the prospective population-based Young ... ...

Abstract	The objective of this study was to investigate (i) whether childhood family SES predicts offspring's compassion between ages 20-50 years and (ii) whether adulthood SES predicts compassion or vice versa. We used the prospective population-based Young Finns data (N = 637-2300). Childhood family SES was evaluated in 1980; participants' adulthood SES in 2001 and 2011; and compassion for others in 1997, 2001, and 2012. Compassion for others was evaluated with the Compassion scale of the Temperament and Character Inventory. The results showed that high childhood family SES (a composite score of educational level, occupational status, unemployment status, and level of income) predicted offspring's higher compassion between ages 30-40 years but not in early adulthood or middle age. These results were obtained independently of a variety of potential confounders (disruptive behavior in childhood; parental mental disorder; frequency of parental alcohol use and alcohol intoxication). Moreover, high compassion for others in adulthood (a composite score of educational level, occupational status, and unemployment status) predicted higher adulthood SES later in their life (after a 10-year follow-up), but not vice versa. In conclusion, favorable socioeconomic environment in childhood appears to have a positive effect on offspring's compassion in their middle adulthood. This effect may attenuate by middle age. High compassion for others seems to promote the achievement of higher SES in adulthood.
Keywords	Medicine ; R ; Science ; Q
Subject code	333
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Age-dependent association of gut bacteria with coronary atherosclerosis

Sari Tuomisto / Heini Huhtala / Mika Martiskainen / Sirkka Goebeler / Terho Lehtimäki / Pekka J Karhunen

PLoS ONE, Vol 14, Iss 8, p e

Tampere Sudden Death Study.

2019 Volume 0221345

Abstract: Background The gut microbiome is thought to remain stable into old age. Gut bacteria and their translocation may play a role in the development of coronary heart disease (CHD) by modulating cholesterol levels and immune responses, as well as by producing ...

Abstract	Background The gut microbiome is thought to remain stable into old age. Gut bacteria and their translocation may play a role in the development of coronary heart disease (CHD) by modulating cholesterol levels and immune responses, as well as by producing toxic metabolites and bacterial endotoxins. The association of changes in the gut microbiome with the severity of coronary atherosclerosis and the ability of gut bacteria themselves to translocate into coronary plaques has not been studied. Materials and methods As a part of the Tampere Sudden Death Study, we measured age-dependent changes in the relative ratios of major intestinal bacterial communities (Bacteroides species [spp.], the Clostridium leptum group, the Clostridium coccoides group, Bifidobacterium spp., Enterobactericeae, Lactobacillus spp.) and Streptococcus spp. in both feces and coronary plaques of the same male autopsy cases (n = 67, age range 44-95) using real-time quantitative PCR (qPCR). The area of coronary atherosclerotic lesions were measured by computer-assisted morphometry. Fecal bacterial DNA measurements from healthy volunteers served as a control for gut bacterial analyses of autopsy cases. The relative amount of bacterial DNA in a sample was determined with the comparative Cq method. Results The relative ratios of fecal Lactobacillus spp., Bifidobacterium spp., the Clostridium coccoides group, and Bacteroides spp. did not differ between controls and autopsy cases and showed no age-dependence. In contrast, the ratios of the Clostridium leptum group, Enterobactericeae, and Streptococcus spp. increased with age. Elevated relative ratios of fecal Enterobactericeae associated with a larger coronary plaque fibrotic area (p = 0.001), and the Clostridium leptum group with a larger calcification area (p = 0.015). Intestinal bacterial DNA could be amplified in 67.6% of the coronary plaques, the most common being Streptococcus spp. (41.0%), followed by Enterobactericeae (12.1%), Clostridium leptum (2.4%), and Lactobacillus spp. (2.4%). The ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Health endowment and later-life outcomes in the labour market

Jaakko Pehkonen / Jutta Viinikainen / Petri Böckerman / Niina Pitkänen / Terho Lehtimäki / Olli Raitakari

SSM: Population Health, Vol 7, Iss , Pp - (2019)

Evidence using genetic risk scores and reduced-form models

2019

Abstract: This paper examines the relationship between health endowment and later-life outcomes in the labour market. The analysis is based on reduced-form models in which labour market outcomes are regressed on genetic variants related to the increased risk of ... ...

Abstract	This paper examines the relationship between health endowment and later-life outcomes in the labour market. The analysis is based on reduced-form models in which labour market outcomes are regressed on genetic variants related to the increased risk of cardiovascular diseases. We use linked Finnish data that have many strengths. Genetic risk scores constitute exogenous measures for health endowment, and accurate administrative tax records on earnings, employment and social income transfers provide a comprehensive account of an individual’s long-term performance in the labour market. The results show that although the direction of an effect is generally consistent with theoretical reasoning, the effects of health endowment on outcomes are statistically weak, and the hypothesis of no effect can be rejected only in one case: genetic endowment related to obesity influences male earnings and employment in prime age. Due to the sample size (N = 1651), the results should be interpreted with caution and should be confirmed in larger samples and in other institutional settings. JEL classification: D62, I1, I12, J01, J24, J3, J7, Keywords: Genetics, Health endowment, Earnings, Employment, Social income transfers, Reduced-form regression
Keywords	Public aspects of medicine ; RA1-1270 ; Social sciences (General) ; H1-99
Subject code	336
Language	English
Publishing date	2019-04-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prevalence and long-term prognostic implications of prolonged QRS duration in left ventricular hypertrophy

Harri Rissanen / Terho Lehtimäki / Leo-Pekka Lyytikäinen / Kjell Nikus / Mika Kähönen / Markku Eskola / Jussi Hernesniemi / Heini Huhtala / Antti Jula / Jani Rankinen / Petri Haataja / Suvi Tuohinen / Andrés Ricardo Pérez-Riera

BMJ Open, Vol 12, Iss

a population-based observational cohort study

2022 Volume 2

Keywords	Medicine ; R
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: C-type lectin receptor CLEC4A2 promotes tissue adaptation of macrophages and protects against atherosclerosis

Inhye Park / Michael E. Goddard / Jennifer E. Cole / Natacha Zanin / Leo-Pekka Lyytikäinen / Terho Lehtimäki / Evangelos Andreakos / Marc Feldmann / Irina Udalova / Ignat Drozdov / Claudia Monaco

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 17

Abstract: The contribution of distinct subsets of macrophages to atherosclerosis is poorly understood. Here the authors describe a protective subset of vascular macrophages expressing the C-type lectin receptor CLEC4A2, which licenses monocytes to join the ... ...

Abstract	The contribution of distinct subsets of macrophages to atherosclerosis is poorly understood. Here the authors describe a protective subset of vascular macrophages expressing the C-type lectin receptor CLEC4A2, which licenses monocytes to join the resident vascular macrophage pool and ensures vascular homeostasis.
Keywords	Science ; Q
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Pancreatic Secretory Trypsin Inhibitor (SPINK1) Gene Mutation in Patients with Acute Alcohol Pancreatitis (AAP) Compared to Healthy Controls and Heavy Alcohol Users without Pancreatitis

Anssi Nikkola / Kari Antero Mäkelä / Karl-Heinz Herzig / Shivaprakash Jagalur Mutt / Aishwarya Prasannan / Hanna Seppänen / Terho Lehtimäki / Mika Kähönen / Olli Raitakari / Ilkka Seppälä / Pihla Pakkanen / Isto Nordback / Juhani Sand / Johanna Laukkarinen

International Journal of Molecular Sciences, Vol 23, Iss 15726, p

2022 Volume 15726

Abstract: Only 3–5% of heavy alcohol users develop acute alcohol pancreatitis (AAP). This suggests that additional triggers are required to initiate the inflammatory process. Genetic susceptibility contributes to the development of AAP, and SPINK1 mutation is a ... ...

Abstract	Only 3–5% of heavy alcohol users develop acute alcohol pancreatitis (AAP). This suggests that additional triggers are required to initiate the inflammatory process. Genetic susceptibility contributes to the development of AAP, and SPINK1 mutation is a documented risk factor. We investigated the prevalence of the SPINK1(N34S) mutation in patients with AAP compared to heavy alcohol users who had never suffered an episode of pancreatitis. Blood samples for the mutational analysis from patients with first episode ( n = 60) and recurrent AAP ( n = 43) and from heavy alcohol users without a history of AAP ( n = 98) as well as from a control population ( n = 1914) were obtained. SPINK1 mutation was found in 8.7% of the patients with AAP. The prevalence was significantly lower in healthy controls (3.4%, OR 2.72; 1.32–5.64) and very low in alcoholics without pancreatitis (1.0%, OR 9.29; 1.15–74.74). In a comparison adjusted for potential cofounders between AAP patients and alcoholics, SPINK1 was found to be an independent marker for AAP. The prevalence of the SPINK1 mutation is overrepresented in AAP patients and very low in alcoholics without pancreatitis. This finding may play a role in understanding the variable susceptibility to AAP found in heavy alcohol users.
Keywords	acute alcohol pancreatitis ; alcoholics ; genetics ; genes ; SPINK1 ; serine protease inhibitor Kazal-type 1 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Circulatory and prostatic tissue lipidomic profiles shifts after high-dose atorvastatin use in men with prostate cancer

Paavo Raittinen / Kati Niemistö / Erika Pennanen / Heimo Syvälä / Seppo Auriola / Jarno Riikonen / Terho Lehtimäki / Pauliina Ilmonen / Teemu Murtola

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 10

Abstract: Abstract Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use ... ...

Abstract	Abstract Prostate cancer patients using cholesterol-lowering statins have 30% lower risk of prostate cancer death compared to non-users. The effect is attributed to the inhibition of the mevalonate pathway in prostate cancer cells. Moreover, statin use causes lipoprotein metabolism changes in the serum. Statin effect on serum or intraprostatic lipidome profiles in prostate cancer patients has not been explored. We studied changes in the serum metabolomic and prostatic tissue lipidome after high-dose 80 mg atorvastatin intervention to expose biological mechanisms causing the observed survival benefit. Our randomized, double-blind, placebo-controlled clinical trial consisted of 103 Finnish men with prostate cancer. We observed clear difference in post-intervention serum lipoprotein lipid profiles between the study arms (median classification error 11.7%). The atorvastatin effect on intraprostatic lipid profile was not as clear (median classification error 44.7%), although slightly differing lipid profiles by treatment arm was observed, which became more pronounced in men who used atorvastatin above the median of 27 days (statin group median classification error 27.2%). Atorvastatin lowers lipids important for adaptation for hypoxic microenvironment in the prostate suggesting that prostate cancer cell survival benefit associated with statin use might be mediated by both, local and systemic, lipidomic/metabolomic profile changes.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Similarity of salivary microbiome in parents and adult children

Kati Sundström / Pashupati P. Mishra / Mikko J. Pyysalo / Terho Lehtimäki / Pekka J. Karhunen / Tanja Pessi

PeerJ, Vol 8, p e

2020 Volume 8799

Abstract: Background Human saliva contains approximately 700 bacterial species. It has been reported that the salivary microbiome of a large family of closely related individuals consisting of multiple households is similar but the relatedness of salivary bacteria ...

Abstract	Background Human saliva contains approximately 700 bacterial species. It has been reported that the salivary microbiome of a large family of closely related individuals consisting of multiple households is similar but the relatedness of salivary bacteria between generations of parents and their children has not yet been investigated. The objectives were to investigate the entirety of salivary bacterial DNA profiles and whether and how families share these profiles and also compare these communities between grandparents and their first daughter generations (F1) using 16S rRNA gene amplicon sequencing. Results The most abundant phyla in two separate families were Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria and Actinobacteria. Family ties explained 13% of the variance between individuals’ bacterial communities (R2 = 0.13; P = 0.001). Mothers shared more OTUs with adult children compared to fathers, but this linkage seemed to be weaker in the nuclear family with older adult children. We identified 29 differentially abundant genus level OTUs (FDR < 0.05) between families, which accounted for 31% of the total identified genus level OTUs. Conclusions Our results indicate that adult family members share bacterial communities and adult children were more similar to mothers than fathers. The observed similarity in oral microbiome between parent–child pairs seemed to weaken over time. We suggest that our analysis approach is suitable for relatedness study of multigenerational salivary bacteria microbiome.
Keywords	Metagenomics ; Next generation sequencing ; Saliva ; Microbiota ; Similarity ; 16S rRNA gene ; Medicine ; R ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Modular genome-wide gene expression architecture shared by early traits of osteoporosis and atherosclerosis in the Young Finns Study

Binisha H. Mishra / Pashupati P. Mishra / Emma Raitoharju / Saara Marttila / Nina Mononen / Harri Sievänen / Jorma Viikari / Markus Juonala / Marika Laaksonen / Nina Hutri-Kähönen / Mika Kähönen / Olli T. Raitakari / Terho Lehtimäki

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and ... ...

Abstract	Abstract We analysed whole blood genome-wide expression data to identify gene co-expression modules shared by early traits of osteoporosis and atherosclerosis. Gene expression was profiled for the Young Finns Study participants. Bone mineral density and content were measured as early traits of osteoporosis. Carotid and bulbus intima media thickness were measured as early traits of atherosclerosis. Joint association of the modules, identified with weighted co-expression analysis, with early traits of the diseases was tested with multivariate analysis. Among the six modules significantly correlated with early traits of both the diseases, two had significant (adjusted p-values (p.adj) < 0.05) and another two had suggestively significant (p.adj < 0.25) joint association with the two diseases after adjusting for age, sex, body mass index, smoking habit, alcohol consumption, and physical activity. The three most significant member genes from the significant modules were NOSIP, GXYLT2, and TRIM63 (p.adj ≤ 0.18). Genes in the modules were enriched with biological processes that have separately been found to be involved in either bone metabolism or atherosclerosis. The gene modules and their most significant member genes identified in this study support the osteoporosis-atherosclerosis comorbidity hypothesis and can provide new joint biomarkers for both diseases and their dual prevention.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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