Imperial College London

ProfessorMarjo-RiittaJarvelin

Faculty of MedicineSchool of Public Health

Chair in Lifecourse Epidemiology
 
 
 
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+44 (0)20 7594 3345m.jarvelin

 
 
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Location

 

156Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
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922 results found

Smith SB, Parisien M, Bair E, Belfer I, Chabot-Doré A-J, Gris P, Khoury S, Tansley S, Torosyan Y, Zaykin DV, Bernhardt O, de Oliveira Serrano P, Gracely RH, Jain D, Järvelin M-R, Kaste LM, Kerr KF, Kocher T, Lähdesmäki R, Laniado N, Laurie CC, Laurie CA, Männikkö M, Meloto CB, Nackley AG, Nelson SC, Pesonen P, Ribeiro-Dasilva MC, Rizzatti-Barbosa CM, Sanders AE, Schwahn C, Sipilä K, Sofer T, Teumer A, Mogil JS, Fillingim RB, Greenspan JD, Ohrbach R, Slade GD, Maixner W, Diatchenko Let al., 2019, Genome-wide association reveals contribution of MRAS to painful temporomandibular disorder in males., Pain, Vol: 160, Pages: 579-591

Painful temporomandibular disorders (TMDs) are the leading cause of chronic orofacial pain, but its underlying molecular mechanisms remain obscure. Although many environmental factors have been associated with higher risk of developing painful TMD, family and twin studies support a heritable genetic component as well. We performed a genome-wide association study assuming an additive genetic model of TMD in a discovery cohort of 999 cases and 2031 TMD-free controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) study. Using logistic models adjusted for sex, age, enrollment site, and race, we identified 3 distinct loci that were significant in combined or sex-segregated analyses. A single-nucleotide polymorphism on chromosome 3 (rs13078961) was significantly associated with TMD in males only (odds ratio = 2.9, 95% confidence interval: 2.02-4.27, P = 2.2 × 10). This association was nominally replicated in a meta-analysis of 7 independent orofacial pain cohorts including 160,194 participants (odds ratio = 1.16, 95% confidence interval: 1.0-1.35, P = 2.3 × 10). Functional analysis in human dorsal root ganglia and blood indicated this variant is an expression quantitative trait locus, with the minor allele associated with decreased expression of the nearby muscle RAS oncogene homolog (MRAS) gene (beta = -0.51, P = 2.43 × 10). Male mice, but not female mice, with a null mutation of Mras displayed persistent mechanical allodynia in a model of inflammatory pain. Genetic and behavioral evidence support a novel mechanism by which genetically determined MRAS expression moderates the resiliency to chronic pain. This effect is male-specific and may contribute to the lower rates of painful TMD in men.

JOURNAL ARTICLE

Ferreira MAR, Vonk JM, Baurecht H, Marenholz I, Tian C, Hoffman JD, Helmer Q, Tillander A, Ullemar V, Lu Y, Rüschendorf F, 23andMe Research Team, SHARE study, Hinds DA, Hübner N, Weidinger S, Magnusson PKE, Jorgenson E, Lee Y-A, Boomsma DI, Karlsson R, Almqvist C, Koppelman GH, Paternoster Let al., 2019, Eleven loci with new reproducible genetic associations with allergic disease risk., J Allergy Clin Immunol, Vol: 143, Pages: 691-699

BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities. OBJECTIVE: We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects. METHODS: We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study. RESULTS: Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10-6. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress TH2 responses. CONCLUSION: Using a gene-based approach, we identified 11 risk loci for allergic disease that were not repo

JOURNAL ARTICLE

Palaniswamy S, Piltonen T, Koiranen M, Mazej D, Järvelin M-R, Abass K, Rautio A, Sebert Set al., 2019, The association between blood copper concentration and biomarkers related to cardiovascular disease risk - analysis of 206 individuals in the Northern Finland Birth Cohort 1966, Journal of Trace Elements in Medicine and Biology, Vol: 51, Pages: 12-18, ISSN: 0946-672X

BACKGROUND: Copper is an abundant trace element in humans where alterations in the circulating concentration could inform on chronic disease aetiology. To date, data are lacking to study how copper may associate with cardiovascular disease (CVD) risk factors in young and healthy population. Molecular evidence suggests an important role of copper in liver metabolism, an essential organ in maintaining cardiovascular health and inflammation, therefore supporting copper as an associated biomarker of the risk. OBJECTIVE: We performed a cross-sectional analysis to examine the possible associations between blood copper levels and risk factors for CVD and pre-inflammatory process. DESIGN: The data has been collected from a sub-sample set of the Northern Finland Birth Cohort 1966 (NFBC1966) at 31 years. PARTICIPANTS: The study included 206 individuals, 116 men and 90 women. To reduce environmental individual variations affecting both copper and the metabolic profile in the study sample, the participants were selected as: i) being born in Finnish Lapland and ii) living in their birth place for the last five years preceding blood sampling. MAIN OUTCOME MEASURES: Fasting blood copper concentration was measured by inductively coupled plasma mass spectrometer. The CVD risk factors included 6 metabolic clusters (30 cardiovascular and pro-inflammatory factors) assessed by nuclear magnetic resonance. Multivariate linear regression analysis was performed to test the linear association between blood copper and 6 metabolic clusters for CVD risk. Associations were assessed under correction for multiple testing. RESULTS: Copper (Cu) levels were comparable in men and women, with no difference between sexes (p-value <0.60). In multiple regression models, sex adjusted, copper was associated with 9 metabolites from 4 metabolic clusters. After adjustment with BMI, copper was associated with 4 metabolites from 3 metabolic clusters: glutamine, beta-hydroxybutyrate, alpha-1-acid glycoprotein

JOURNAL ARTICLE

Parmar P, Lowry E, Cugliari G, Suderman M, Wilson R, Karhunen V, Andrew T, Wiklund P, Wielscher M, Guarrera S, Teumer A, Lehne B, Milani L, de Klein N, Mishra PP, Melton PE, Mandaviya PR, Kasela S, Nano J, Zhang W, Zhang Y, Uitterlinden AG, Peters A, Schoettker B, Gieger C, Anderson D, Boomsma D, Grabe HJ, Panico S, Veldink JH, van Meurs JBJ, van den Berg L, Beilin LJ, Franke L, Loh M, van Greevenbroek MMJ, Nauck M, Kahonen M, Hurme MA, Raitakari OT, Franco OH, Slagboom PE, van der Harst P, Kunze S, Felix SB, Zhang T, Chen W, Mori TA, Bonnefond A, Heijmans BT, Muka T, Kooner JS, Fischer K, Waldenberger M, Froguel P, Huang R-C, Lehtimaki T, Rathmann W, Relton CL, Matullo G, Brenner H, Verweij N, Li S, Chambers JC, Jarvelin M-R, Sebert Set al., 2018, Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults, EBioMedicine, Vol: 38, Pages: 206-216, ISSN: 2352-3964

BackgroundDNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health.MethodsWe meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL—C), triglycerides (TG), diastolic, and systolic blood pressure (BP).FindingsLower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 × 10−7 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10−8 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels.InterpretationEpigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors.

JOURNAL ARTICLE

Ollila M-ME, Kaikkonen K, Järvelin M-R, Huikuri HV, Tapanainen JS, Franks S, Piltonen TT, Morin-Papunen Let al., 2018, Self-reported polycystic ovary syndrome is associated with hypertension: a Northern Finland Birth Cohort 1966 Study, Journal of Clinical Endocrinology and Metabolism, ISSN: 0021-972X

Context: PCOS is associated with many traditional cardiovascular disease risk factors, but it is unclear whether PCOS is an independent risk factor for hypertension. Objective: To investigate in a population-based set-up whether PCOS associates with the risk of hypertension independently of body-mass-index (BMI), and with cardiovascular manifestations. Design: Cross-sectional assessments in the Northern Finland Birth Cohort 1966 at ages 31 and 46. Setting: General community. Participants: Women who reported both oligo/amenorrhea and hirsutism at age 31 and/or diagnosis of PCOS by age 46 (self-reported PCOS [srPCOS], n=279) and women without PCOS symptoms or diagnosis (n=1577). Intervention: None. Main Outcome Measures: Blood pressure (BP), BMI, cardiovascular manifestations. Results: Use of antihypertensive medication was significantly more common in women with srPCOS. At age 31, women with srPCOS had significantly higher systolic (SBP) and diastolic BP (DBP) than control women (SBP: normal-weight: 119.9±13.2 vs. 116.9±11.4mmHg, P=0.017; overweight/obese: 126.1±14.3 vs. 123.0±11.9mmHg, P=0.031; and DBP: normal-weight: 75.5±10.0 vs. 72.4±9.6mmHg, P=0.003; overweight/obese: 80.7±11.8 vs. 78.0±10.6mmHg, P=0.031). At age 46, srPCOS was significantly associated with hypertension (AOR=1.56 [1.14-2.13]) independently of BMI, and with higher cardiovascular morbidity (6.8% vs. 3.4%, P=0.011). Hypertensive srPCOS displayed consistent, unfavorable changes in cardiac structure and function compared with controls. Conclusion: Women with srPCOS displayed higher BP compared with controls already at early age and srPCOS was associated with hypertension independently of overweight/obesity. srPCOS was associated with increased cardiovascular morbidity in premenopausal women, suggesting that cardiovascular disease risk factors should be screened and efficiently managed early enough in women with PCOS.

JOURNAL ARTICLE

Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, Ntritsos G, Dimou N, Cabrera CP, Karaman I, Fu LN, Evangelou M, Witkowska K, Tzanis E, Hellwege JN, Giri A, Edwards DRV, Sun YV, Cho K, Gaziano JM, Wilson PWF, Tsao PS, Kovesdy CP, Esko T, Magi R, Milani L, Almgren P, Boutin T, Debette S, Ding J, Giulianini F, Holliday EG, Jackson AU, Li-Gao R, Lin W-Y, Luan J, Mangino M, Oldmeadow C, Prins BP, Qian Y, Sargurupremraj M, Shah N, Surendran P, Theriault S, Verweij N, Willems SM, Zhao J-H, Amouyel P, Connell J, de Mutsert R, Doney ASF, Farrall M, Menni C, Morris AD, Noordam R, Pare G, Poulter NR, Shields DC, Stanton A, Thom S, Abecasis G, Amin N, Arking DE, Ayers KL, Barbieri CM, Batini C, Bis JC, Blake T, Bochud M, Boehnke M, Boerwinkle E, Boomsma DI, Bottinger EP, Braund PS, Brumat M, Campbell A, Campbell H, Chakravarti A, Chambers JC, Chauhan G, Ciullo M, Cocca M, Collins F, Cordell HJ, Davies G, de Borst MH, de Geus EJ, Deary IJ, Deelen J, Del Greco FM, Demirkale CY, Dorr M, Ehret GB, Elosua R, Enroth S, Erzurumluoglu AM, Ferreira T, Franberg M, Franco OH, Gandin I, Gasparini P, Giedraitis V, Gieger C, Girotto G, Goel A, Gow AJ, Gudnason V, Guo X, Gyllensten U, Hamsten A, Harris TB, Harris SE, Hartman CA, Havulinna AS, Hicks AA, Hofer E, Hofman A, Hottenga J-J, Huffman JE, Hwang S-J, Ingelsson E, James A, Jansen R, Jarvelin M-R, Joehanes R, Johansson A, Johnson AD, Joshi PK, Jousilahti P, Jukema JW, Jula A, Kahonen M, Kathiresan S, Keavney BD, Khaw K-T, Knekt P, Knight J, Kolcic I, Kooner JS, Koskinen S, Kristiansson K, Kutalik Z, Laan M, Larson M, Launer LJ, Lehne B, Lehtimaki T, Liewald DCM, Lin L, Lind L, Lindgren CM, Liu Y, Loos RJF, Lopez LM, Lu Y, Lyytikainen L-P, Mahajan A, Mamasoula C, Marrugat J, Marten J, Milaneschi Y, Morgan A, Morris AP, Morrison AC, Munson PJ, Nalls MA, Nandakumar P, Nelson CP, Niiranen T, Nolte IM, Nutile T, Oldehinkel AJ, Oostra BA, O'Reilly PF, Org E, Padmanabhan S, Palmas W, Palotie A, Pattie A, Penninx BWJH, Perolet al., 2018, Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018), NATURE GENETICS, Vol: 50, Pages: 1755-1755, ISSN: 1061-4036

JOURNAL ARTICLE

Ramsay H, Barnett JH, Murray GK, Miettunen J, Maki P, Jarvelin M-R, Smith GD, Ala-Korpela M, Veijola Jet al., 2018, Cognition, psychosis risk and metabolic measures in two adolescent birth cohorts, PSYCHOLOGICAL MEDICINE, Vol: 48, Pages: 2609-2623, ISSN: 0033-2917

JOURNAL ARTICLE

Ramsay H, Barnett JH, Murray GK, Miettunen J, Maki P, Jarvelin M-R, Smith GD, Ala-Korpela M, Veijola Jet al., 2018, Cognition, psychosis risk and metabolic measures in two adolescent birth cohorts (vol 48, pg 2609, 2018), PSYCHOLOGICAL MEDICINE, Vol: 48, Pages: 2628-2628, ISSN: 0033-2917

JOURNAL ARTICLE

Ligthart S, Vaez A, Vosa U, Stathopoulou MG, de Vries PS, Prins BP, Van der Most PJ, Tanaka T, Naderi E, Rose LM, Wu Y, Karlsson R, Barbalic M, Lin H, Pool R, Zhu G, Mace A, Sidore C, Trompet S, Mangino M, Sabater-Lleal M, Kemp JP, Abbasi A, Kacprowski T, Verweij N, Smith AV, Huang T, Marzi C, Feitosa MF, Lohman KK, Kleber ME, Milaneschi Y, Mueller C, Huq M, Vlachopoulou E, Lyytikainen L-P, Oldmeadow C, Deelen J, Perola M, Zhao JH, Feenstra B, Amini M, Lahti J, Schraut KE, Fornage M, Suktitipat B, Chen W-M, Li X, Nutile T, Malerba G, Luan J, Bak T, Schork N, Del Greco FM, Thiering E, Mahajan A, Marioni RE, Mihailov E, Eriksson J, Ozel AB, Zhang W, Nethander M, Cheng Y-C, Aslibekyan S, Ang W, Gandin I, Yengo L, Portas L, Kooperberg C, Hofer E, Rajan KB, Schurmann C, den Hollander W, Ahluwalia TS, Zhao J, Draisma HHM, Ford I, Timpson N, Teumer A, Huang H, Wahl S, Liu Y, Huang J, Uh H-W, Geller F, Joshi PK, Yanek LR, Trabetti E, Lehne B, Vozzi D, Verbanck M, Biino G, Saba Y, Meulenbelt I, O'Connell JR, Laakso M, Giulianini F, Magnusson PKE, Ballantyne CM, Hottenga JJ, Montgomery G, Rivadineira F, Rueedi R, Steri M, Herzig K-H, Stott DJ, Menni C, Franberg M, St Pourcain B, Felix SB, Pers TH, Bakker SJL, Kraft P, Peters A, Vaidya D, Delgado G, Smit JH, Grossmann V, Sinisalo J, Seppala I, Williams SR, Holliday EG, Moed M, Langenberg C, Raikkonen K, Ding J, Campbell H, Sale MM, Chen Y-DI, James AL, Ruggiero D, Soranzo N, Hartman CA, Smith EN, Berenson GS, Fuchsberger C, Hernandez D, Tiesler CMT, Giedraitis V, Liewald D, Fischer K, Mellstrom D, Larsson A, Wang Y, Scott WR, Lorentzon M, Beilby J, Ryan KA, Pennell CE, Vuckovic D, Balkau B, Concas MP, Schmidt R, de Leon CFM, Bottinger EP, Kloppenburg M, Paternoster L, Boehnke M, Musk AW, Willemsen G, Evans DM, Madden PAF, Kahonen M, Kutalik Z, Zoledziewska M, Karhunen V, Kritchevsky SB, Sattar N, Lachance G, Clarke R, Harris TB, Raitakari OT, Attia JR, Van Heemst D, Kajantie E, Sorice R, Gambaro G, Scott RA, Hicks AA, Ferrucciet al., 2018, Genome analyses of >200,000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders, American Journal of Human Genetics, Vol: 103, Pages: 691-706, ISSN: 0002-9297

C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10−8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

JOURNAL ARTICLE

Nasanen-Gilmore P, Sipola-Leppanen M, Tikanmaki M, Matinolli H-M, Eriksson JG, Jarvelin M-R, Vaarasmaki M, Hovi P, Kajantie Eet al., 2018, Lung function in adults born preterm, PLOS ONE, Vol: 13, ISSN: 1932-6203

JOURNAL ARTICLE

Evensen KAI, Tikanmäki M, Heinonen K, Matinolli H-M, Sipola-Leppänen M, Lano A, Wolke D, Vääräsmäki M, Eriksson JG, Andersson S, Järvelin M-R, Hovi P, Räikkönen K, Kajantie Eet al., 2018, Musculoskeletal pain in adults born preterm: evidence from two birth cohort studies, European Journal of Pain, ISSN: 1532-2149

BackgroundIndividuals born preterm are at risk of later developmental problems and long‐term morbidities. There is conflicting evidence regarding musculoskeletal pain in young adulthood. We investigated the prevalence of self‐reported musculoskeletal pain in young adults born across the range of preterm birth compared with a term‐born reference group.MethodsFrom two Finnish birth cohorts, 184 individuals born early preterm (<34 weeks), 350 late preterm (34 to <37 weeks) and 641 at term completed a self‐report questionnaire of musculoskeletal pain at mean age 24.1 (SD: 1.4) years. Group differences were examined by logistic regression models adjusting for sex, age and cohort (Model 1), potential early life confounders (Model 2) and lifestyle factors related to physical (Model 3) and mental health (Model 4).ResultsThe late preterm group had lower odds for reporting neck pain (0.73; 95% confidence interval (CI): 0.56–0.96), which was further reduced when adjusting for early life confounders and lifestyle factors (Model 4). Odds for reporting peripheral pain were 0.69 (95% CI: 0.48–0.99, Model 4) in the early preterm group. The odds for reporting any pain, shoulder, low back or widespread pain did not differ significantly between groups, although odds for reporting widespread pain were 0.77 (95% CI: 0.58–1.03, Model 4) in the late preterm group.ConclusionsWe did not find evidence of increased prevalence of musculoskeletal pain in adults born early or late preterm. In contrast, our results suggest that adults born preterm have a slightly lower risk of reporting musculoskeletal pain, also when we adjusted for lifestyle factors.SignificanceYoung adults born preterm do not have increased rates of musculoskeletal pain. Our findings rather suggest that these rates may be slightly lower than among those born at term.

JOURNAL ARTICLE

Balkhiyarova Z, Kaakinen MA, Draisma HHM, Timonen M, Veijola J, Jarvelin M-R, Nouwen A, Prokopenko Iet al., 2018, Dissecting shared pathophysiology of type 2 diabetes and depressive symptoms using multi-phenotype genome-wide association study, 54th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S128-S128, ISSN: 0012-186X

CONFERENCE PAPER

Karhunen V, Wiklund P, Jarvelin M-R, Rodriguez Aet al., 2018, Joint genetic factors of body mass index and ADHD components, 27th Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), Publisher: WILEY, Pages: 709-709, ISSN: 0741-0395

CONFERENCE PAPER

Kaakinen M, Prelot L, Draisma H, Anasanti MD, Jarvelin M-R, Prokopenko Iet al., 2018, Machine learning in multi-omics data to assess longitudinal predictors of glycaemic trait levels, 27th Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), Publisher: WILEY, Pages: 709-709, ISSN: 0741-0395

CONFERENCE PAPER

Anasanti MD, Kaakinen M, Jarvelin M-R, Prokopenko Iet al., 2018, Addressing the missing data issue in multi-phenotype genome-wide association studies, 27th Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), Publisher: WILEY, Pages: 686-686, ISSN: 0741-0395

CONFERENCE PAPER

Draisma H, Kaakinen M, Prelot L, Anasanti MD, Balkhiyarova Z, Wielscher M, Sebert S, Jarvelin M-R, Prokopenko Iet al., 2018, Epigenome-wide association study of change in body mass index from young- to middle adulthood in 626 northern Finland birth cohort 1966 participants, 27th Annual Meeting of the International-Genetic-Epidemiology-Society (IGES), Publisher: WILEY, Pages: 724-725, ISSN: 0741-0395

CONFERENCE PAPER

Macare C, Ducci F, Zhang Y, Ruggeri B, Jia T, Kaakinen M, Kalsi G, Charoen P, Casoni F, Peters J, Bromberg U, Hil M, Buxton J, Blakemore A, Veijola J, Buchel C, Banaschewski T, Bokde ALW, Conrod P, Flor H, Frouin V, Gallinat J, Garavan H, Gowland PA, Heinz A, Itternnann B, Lathrop M, Martinot J-L, Paus T, Desrivieres S, Munafo M, Jarvelin M-R, Schumanna Get al., 2018, A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants and reward response, EUROPEAN NEUROPSYCHOPHARMACOLOGY, Vol: 28, Pages: 1103-1114, ISSN: 0924-977X

JOURNAL ARTICLE

Ramzi NH, Yiorkas AM, Sebert S, Keinanen-Kiukaanniemi S, Ala-Mursula L, Svento R, Jokelainen J, Veijola J, Auvinen J, Miettunen J, Dovey TM, Jarvelin M-R, Blakemore AIFet al., 2018, Relationship between BMI and emotion-handling capacity in an adult Finnish population: the Northern Finland Birth Cohort 1966, PLoS ONE, Vol: 13, ISSN: 1932-6203

BackgroundAlexithymia, a difficulty in identifying and expressing emotions, has been associated with obesity and eating disorders in small-scale cross-sectional studies. Here, we assess the relationship between body mass index (BMI) and alexithymia in a large cohort of free-living Finnish adults over a 15-year period.MethodsParticipants were drawn from the Northern Finnish Birth Cohort 1966 (NFBC1966). The 20-Item Toronto Alexithymia Scale (TAS-20) was used as a measure of alexithymia and was completed at the age of 31 years (31y: n = 4841), and 46 years (46y: n = 5404). BMI was recorded at both time points. Where data at both time points were available (n = 3274), the relationship between changes in BMI and TAS-20 over this time period was also investigated.ResultsBMI was significantly and positively associated with TAS-20 score (p<0.0001, both at 31 years and at 46 years of ages). The association remained statistically significant after adjustment for potential confounders (sex, marital status and several socio-economic indicators). In individuals who experienced the greatest change in BMI (in either direction) over the 15-year period, there was a modest mean increase in TAS-20 score.ConclusionsOur data revealed that TAS-20 score was correlated with and co-varied with body mass status. We suggest that future clinical research should consider the role of alexithymia in obesity. Further investigation of this relationship is warranted to ensure that the needs of obese subjects with undiagnosed alexithymia are considered in the design of weight management programmes.

JOURNAL ARTICLE

Evangelou E, Elliott P, Tzoulaki I, Pazoki R, Karaman I, Gao H, Mosen-Ansorena D, Evangelou M, Jarvelin M, Poulter NR, Thom SAM, Kooner JS, Sever PS, Chambers JCet al., 2018, Genetic analysis of over one million people identifies 535 new loci associated with blood pressure traits, Nature Genetics, ISSN: 1061-4036

High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

JOURNAL ARTICLE

Hüls A, Klümper C, MacIntyre EA, Brauer M, Melén E, Bauer M, Berdel D, Bergström A, Brunekreef B, Chan-Yeung M, Fuertes E, Gehring U, Gref A, Heinrich J, Standl M, Lehmann I, Kerkhof M, Koppelman GH, Kozyrskyj AL, Pershagen G, Carlsten C, Krämer U, Schikowski T, TAG Study Groupet al., 2018, Atopic dermatitis: Interaction between genetic variants of GSTP1, TNF, TLR2 & TLR4 and air pollution in early life, Pediatric Allergy and Immunology, Vol: 29, Pages: 596-605, ISSN: 1399-3038

BACKGROUND: Associations between traffic-related air pollution (TRAP) and childhood atopic dermatitis (AD) remain inconsistent, possibly due to unexplored gene-environment interactions. The aim of this study was to examine whether a potential effect of TRAP on AD prevalence in children is modified by selected single nucleotide polymorphisms (SNPs) related to oxidative stress and inflammation. METHODS: Doctor-diagnosed AD up to age 2 years and at 7-8 years, as well as AD symptoms up to age 2 years, were assessed using parental-reported questionnaires in six birth cohorts (N=5,685). Associations of nitrogen dioxide (NO2) estimated at the home address of each child at birth, and nine SNPs within the GSTP1, TNF, TLR2, or TLR4 genes with AD were examined. Weighted genetic risk scores (GRS) were calculated from the above SNPs and used to estimate combined marginal genetic effects of oxidative stress and inflammation on AD and its interaction with TRAP. RESULTS: GRS was associated with childhood AD and modified the association between NO2 and doctor-diagnosed AD up to the age of 2 years (p(interaction)=0.029). This interaction was mainly driven by a higher susceptibility to air pollution in TNF rs1800629 minor allele (A) carriers. TRAP was not associated with the prevalence of AD in the general population. CONCLUSIONS: The marginal genetic association of a weighted GRS from GSTP1, TNF, TLR2, and TLR4 SNPs and its interaction with air pollution supports the role of oxidative stress & inflammation in AD. This article is protected by copyright. All rights reserved.

JOURNAL ARTICLE

Wielscher M, Amaral AFS, Jarvelin M, Jarvis Det al., 2018, SERPINA1 methylation and lung function in tobacco-smoke exposed European children and adults: a meta-analysis of ALEC population-based cohorts, Respiratory Research, Vol: 19, ISSN: 1465-9921

BackgroundThe pathophysiological role of SERPINA1 in respiratory health may be more strongly determined by the regulation of its expression than by common genetic variants. A family based study of predominantly smoking adults found methylation at two Cytosine-phosphate-Guanine sites (CpGs) in SERPINA1 gene to be associated with chronic obstructive pulmonary disease risk. The objective of this study was to confirm the association of lung function with SERPINA1 methylation in general population samples by testing a comprehensive set of CpGs in the SERPINA gene cluster. We considered lung function level and decline in adult smokers from three European population-based cohorts and lung function level and growth in tobacco-smoke exposed children from a birth cohort.MethodsDNA methylation using Illumina Infinium Human Methylation 450 k and EPIC beadchips and lung function were measured at two time points in 1076 SAPALDIA, ECRHS and NFBC adult cohort participants and 259 ALSPAC children. Associations of methylation at 119 CpG sites in the SERPINA gene cluster (PP4R4-SERPINA13P) with lung functions and circulating alpha-1-antitripsin (AAT) were assessed using multivariable cross-sectional and longitudinal regression models.ResultsMethylation at cg08257009 in the SERPINA gene cluster, located 32 kb downstream of SERPINA1, not annotated to a gene, was associated with FEV1/FVC at the Bonferroni corrected level in adults, but not in children. None of the methylation signals in the SERPINA1 gene showed associations with lung function after correcting for multiple testing.ConclusionsThe results do not support a role of SERPINA1 gene methylation as determinant of lung function across the life course in the tobacco smoke exposed general population exposed.

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Lowry E, Rautio N, Karhunen V, Miettunen J, Ala-Mursula L, Auvinen J, Keinänen-Kiukaanniemi S, Puukka K, Prokopenko I, Herzig K, Lewin A, Sebert S, Jarvelin Met al., 2018, Understanding the complexity of glycaemic health - Systematic bio-psychosocial modelling of fasting glucose in middle-age adults; a DynaHEALTH study, International Journal of Obesity, ISSN: 0307-0565

Abstract BackgroundThe prevention of the risk of type 2 diabetes (T2D) is complicated by multidimensional interplays between biological and psychosocial factors acting at the individual level. To address the challenge we took a systematic approach, to explore the bio-psychosocial predictors of blood glucose in mid-age.MethodsBased on the 31- and 46-year follow-ups (5,078 participants, 43% male) of Northern Finland Birth Cohort 1966, we used a systematic strategy to select bio-psychosocial variables at 31 years to enable a data-driven approach. As selection criteria, the variable must be i) a component of the metabolic syndrome or an indicator of psychosocial health using WHO guidelines, ii) easily obtainable in general health check-ups and iii) associated with fasting blood glucose at 46 years (p<0.10). Exploratory and confirmatory factor analysis were used to derive latent factors, and stepwise linear regression allowed exploration of relationships between factors and fasting glucose.ResultsOf all 26 variables originally considered, 19 met selection criteria and were included in an exploratory factor analysis. Two variables were further excluded due to low loading (<0.3). We derived four latent factors, which we named as socioeconomic, metabolic, psychosocial and blood pressure status. The combination of metabolic and psychosocial factors, adjusted for sex, provided best prediction of fasting glucose at 46 years (explaining 10.7% of variation in glucose; P<0.001). Regarding different bio-psychosocial pathways and relationships, the importance of psychosocial factors in addition to established metabolic risk factors was highlighted.ConclusionsThe present study supports evidence for the bio-psychosocial nature of adult glycemic health and exemplifies an evidence-based approach to model the bio-psychosocial relationships. The factorial model may help further research and public health practice in focusing also on psychosocial aspects in maintaining normoglyca

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Waage J, Standl M, Curtin JA, Jessen LE, Thorsen J, Tian C, Schoettler N, 23andMe Research Team, AAGC collaborators, Flores C, Abdellaoui A, Ahluwalia TS, Alves AC, Amaral AFS, Antó JM, Arnold A, Barreto-Luis A, Baurecht H, van Beijsterveldt CEM, Bleecker ER, Bonàs-Guarch S, Boomsma DI, Brix S, Bunyavanich S, Burchard EG, Chen Z, Curjuric I, Custovic A, den Dekker HT, Dharmage SC, Dmitrieva J, Duijts L, Ege MJ, Gauderman WJ, Georges M, Gieger C, Gilliland F, Granell R, Gui H, Hansen T, Heinrich J, Henderson J, Hernandez-Pacheco N, Holt P, Imboden M, Jaddoe VWV, Jarvelin M-R, Jarvis DL, Jensen KK, Jónsdóttir I, Kabesch M, Kaprio J, Kumar A, Lee Y-A, Levin AM, Li X, Lorenzo-Diaz F, Melén E, Mercader JM, Meyers DA, Myers R, Nicolae DL, Nohr EA, Palviainen T, Paternoster L, Pennell CE, Pershagen G, Pino-Yanes M, Probst-Hensch NM, Rüschendorf F, Simpson A, Stefansson K, Sunyer J, Sveinbjornsson G, Thiering E, Thompson PJ, Torrent M, Torrents D, Tung JY, Wang CA, Weidinger S, Weiss S, Willemsen G, Williams LK, Ober C, Hinds DA, Ferreira MA, Bisgaard H, Strachan DP, Bønnelykke Ket al., 2018, Author correction: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis, Nature Genetics, ISSN: 1061-4036

In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.

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Lee JJ, Wedow R, Okbay A, Kong E, Maghzian O, Zacher M, Tuan AN-V, Bowers P, Sidorenko J, Linner RK, Fontana MA, Kundu T, Lee C, Li H, Li R, Royer R, Timshel PN, Walters RK, Willoughby EA, Yengo L, Alver M, Bao Y, Clark DW, Day FR, Furlotte NA, Joshi PK, Kemper KE, Kleinman A, Langenberg C, Magi R, Trampush JW, Verma SS, Wu Y, Lam M, Zhao JH, Zheng Z, Boardman JD, Campbell H, Freese J, Harris KM, Hayward C, Herd P, Kumari M, Lencz T, Luan J, Malhotra AK, Metspalu A, Milani L, Ong KK, Perry JRB, Porteous DJ, Ritchie MD, Smart MC, Smith BH, Tung JY, Wareham NJ, Wilson JF, Beauchamp JP, Conley DC, Esko T, Lehrer SF, Magnusson PKE, Oskarsson S, Pers TH, Robinson MR, Thom K, Watson C, Chabris CF, Meyer MN, Laibson DI, Yang J, Johannesson M, Koellinger PD, Turley P, Visscher PM, Benjamin DJ, Cesarini Det al., 2018, Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals, NATURE GENETICS, Vol: 50, Pages: 1112-+, ISSN: 1061-4036

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Pluymen LPM, Wijga AH, Gehring U, Koppelman GH, Smit HA, van Rossem Let al., 2018, Early introduction of complementary foods and childhood overweight in breastfed and formula-fed infants in the Netherlands: the PIAMA birth cohort study., Eur J Nutr, Vol: 57, Pages: 1985-1993

PURPOSE: To investigate whether early introduction of complementary foods (CF) is associated with an increased risk of overweight during childhood, and whether this association differs between formula-fed and breastfed infants. METHODS: We included 2611 participants that were born at term from a Dutch population-based birth cohort (n = 3963) designed to investigate the development of asthma and allergies. Parents kept records of their infant's age when CF were first introduced. Weight and height were parent reported yearly from age 1 to 8 years, and at ages 11, 14 and 17 years. We used multivariate generalized estimating equations analysis to investigate the association between timing of CF introduction (before 4 months vs at or after 4 months of age) and overweight at ages 1-17 years. RESULTS: Children with CF introduction before 4 months had higher odds of being overweight during childhood than children with CF introduction at or after 4 months (OR 1.32, 95% CI 1.19, 1.47). This association was observed in formula-fed infants (OR 1.51, 95% CI 1.17, 1.94) and breastfed infants (OR 1.32, 95% CI 1.19, 1.47). The duration of breastfeeding modified the association between CF introduction and overweight: children breastfed for shorter than 4 months, but not children breastfed for 4 months or longer with CF introduction before 4 months had higher odds of being overweight (OR 1.37, 95% CI 1.19, 1.57 and 1.07, 95% CI 0.87, 1.32, respectively), compared to those with CF introduction at or after 4 months. CONCLUSIONS: In children born at term, formula-fed infants and infants who were breastfed for shorter than 4 months, but not infants who were breastfed for 4 months or longer, had a higher risk of being overweight during childhood when being introduced to CF before 4 months of age.

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Yang Y, Zhao H, Boomsma DI, Ligthart L, Belin AC, Smith GD, Esko T, Freilinger TM, Hansen TF, Ikram MA, Kallela M, Kubisch C, Paraskevi C, Strachan DP, Wessman M, International Headache Genetics Consortium, van den Maagdenberg AMJM, Terwindt GM, Nyholt DRet al., 2018, Molecular genetic overlap between migraine and major depressive disorder., Eur J Hum Genet, Vol: 26, Pages: 1202-1216

Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h2 = 12%) and MDD (h2 = 19%), and a significant cross-disorder genetic correlation (rG = 0.25; P = 0.04). Meta-analysis of results for 8,045,569 SNPs from a migraine GWAS (comprising 30,465 migraine cases and 143,147 control samples) and the top 10,000 SNPs from a MDD GWAS (comprising 75,607 MDD cases and 231,747 healthy controls), implicated three SNPs (rs146377178, rs672931, and rs11858956) with novel genome-wide significant association (PSNP ≤ 5 × 10-8) to migraine and MDD. Moreover, gene-based association analyses revealed significant enrichment of genes nominally associated (Pgene-based ≤ 0.05) with both migraine and MDD (Pbinomial-test = 0.001). Combining results across migraine and MDD, two genes, ANKDD1B and KCNK5, produced Fisher's combined gene-based P values that surpassed the genome-wide significance threshold (PFisher's-combined ≤ 3.6 × 10-6). Pathway analysis of genes with PFisher's-combined ≤ 1 × 10-3 suggested several pathways, foremost neural-related pathways of signalling and ion channel regulation, to be involved in migraine and MDD aetiology. In conclusion, our study provides strong molecular genetic support for shared genetically determined biological mechanisms underlying migraine and MDD.

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Waage J, Standl M, Curtin JA, Jessen L, Thorsen J, The 23andMe Research Team, AAGC Collaborators, Abdellaoui A, Ahluwalia TS, Alves A, Amaral AFS, Anto JM, Arnold A, Flores C, Baurecht H, Beijstervedldt TCEM, Bleecker ER, Bonas-Guarch S, Boomsma D, Brix S, Bunyavanich S, Burchard E, Chen Z, Curjuric I, Custovic A, den Dekker M, Dharmage SC, Dmitrieva J, Duijts L, Ege M, Barreto-Luis A, Gauderman WJ, Georges M, Gieger C, Gilliland F, Granell R, Gui H, Hansen T, Heinrich J, Henderson J, Hernandez-Pacheco N, Hinds DA, Holt P, Imboden M, Jaddoe V, Jarvelin M, Jarvis D, Jensen KK, Jonsdottir I, Kabesch M, Kaprio J, Kumar A, Lee Y, Levin AM, Li X, Lorenz-Diaz F, Melen E, Mercader JM, Meyers DA, Nicolae DL, Nohr E, Palvianinen T, Paternoster L, Pennell C, Pershagen G, Pino-Yanes M, Probst-Hensch NM, Ruschendorf F, Schoettler N, Simpson A, Stefansson K, Sunyer J, Sveinbjornsson G, Thiering E, Thompson PJ, Tian C, Torrent M, Torrents D, Tung JY, Wang C, Weidinger S, Weiss S, Willemsen G, Williams LK, Ober C, Ferreira MA, Bisgaard H, Strachan D, Bonnelykke Ket al., 2018, Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis, Nature Genetics, ISSN: 1061-4036

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, and with increasing incidence in westernized countries.1,2 To elucidate the genetic architecture and understand disease mechanisms of allergic rhinitis, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implied genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants of importance for antigen binding. We further performed GWASs of allergic sensitization against inhalant allergens and non-allergic rhinitis suggesting shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.

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Karjula S, Morin-Papunen L, Auvinen J, Franks S, Jarvelin MR, Tapanainen J, Jokelainen J, Miettunen J, Piltonen Tet al., 2018, Long-term health related quality of life (HRQoL), life satisfaction and health status in women with PCOS-a population-based follow-up analysis at ages 31 and 46, 34th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Publisher: OXFORD UNIV PRESS, Pages: 444-445, ISSN: 0268-1161

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Pettersson ME, Koppelman GH, Flokstra-de Blok BMJ, Kollen BJ, Dubois AEJet al., 2018, Prediction of the severity of allergic reactions to foods, Allergy: European Journal of Allergy and Clinical Immunology, Vol: 73, Pages: 1532-1540, ISSN: 0105-4538

© 2018 The Authors. Allergy published by John Wiley & Sons Ltd. Background: There is currently considerable uncertainty regarding what the predictors of the severity of diagnostic or accidental food allergic reactions are, and to what extent the severity of such reactions can be predicted. Objective: To identify predictors for the severity of diagnostic and accidental food allergic reactions and to quantify their impact. Methods: The study population consisted of children with a double-blind, placebo-controlled food challenge (DBPCFC)–confirmed food allergy to milk, egg, peanut, cashew nut, and/or hazelnut. The data were analyzed using multiple linear regression analysis. Missing values were imputed using multiple imputation techniques. Two scoring systems were used to determine the severity of the reactions. Results: A total of 734 children were included. Independent predictors for the severity of the DBPCFC reaction were age (B = 0.04, P =.001), skin prick test ratio (B = 0.30, P <.001), eliciting dose (B = −0.09, P <.001), level of specific immunoglobulin E (B = 0.15, P <.001), reaction time during the DBPCFC (B = −0.01, P =.004), and severity of accidental reaction (B = 0.08, P =.015). The total explained variance of this model was 23.5%, and the eliciting dose only contributed 4.4% to the model. Independent predictors for more severe accidental reactions with an explained variance of 7.3% were age (B = 0.03, P =.014), milk as causative food (B = 0.77, P <.001), cashew as causative food (B = 0.54, P <.001), history of atopic dermatitis (B = −0.47, P =.006), and severity of DBPCFC reaction (B = 0.12, P =.003). Conclusions: The severity of DBPCFCs and accidental reactions to food remains largely unpredictable. Clinicians should not use the eliciting dose obtained from a graded food challenge for the purposes of making risk-related management decisions.

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Laru J, Nedelec R, Ojaniemi M, Jarvelin MR, Tapanainen JS, Franks S, Sebert S, Piltonen TT, Morin-Papunen Let al., 2018, Childhood and adolescence body mass index associates with impaired reproductive function - a prospective, population-based cohort study, 34th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology (ESHRE), Publisher: OXFORD UNIV PRESS, Pages: 448-449, ISSN: 0268-1161

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