Imperial College London

ProfessorMarjo-RiittaJarvelin

Faculty of MedicineSchool of Public Health

Chair in Lifecourse Epidemiology
 
 
 
//

Contact

 

+44 (0)20 7594 3345m.jarvelin

 
 
//

Location

 

156Norfolk PlaceSt Mary's Campus

//

Summary

 

Publications

Publication Type
Year
to

976 results found

Metrustry SJ, Karhunen V, Edwards MH, Menni C, Geisendorfer T, Huber A, Reichel C, Dennison EM, Cooper C, Spector T, Jarvelin M-R, Valdes AMet al., 2018, Metabolomic signatures of low birthweight: pathways to insulin resistance and oxidative stress, PLoS ONE, Vol: 13, ISSN: 1932-6203

Several studies suggest that low birthweight resulting from restricted intrauterine growth can leave a metabolic footprint which may persist into adulthood. To investigate this, we performed metabolomic profiling on 5036 female twins, aged 18–80, with weight at birth information available from the TwinsUK cohort and performed independent replication in two additional cohorts. Out of 422 compounds tested, 25 metabolites associated with birthweight in these twins, replicated in 1951 men and women from the Hertfordshire Cohort Study (HCS, aged 66) and in 2391 men and women from the North Finland Birth 1986 cohort (NFBC, aged 16). We found distinct heterogeneity between sexes and, after adjusting for multiple tests and heterogeneity, two metabolites were reproducible overall (propionylcarnitine and 3-4-hydroxyphenyllactate). Testing women only, we found other metabolites associated with lower birthweight from the meta-analysis of the three cohorts (2-hydroxy-butyric acid and γ-glutamylleucine). Higher levels of all these metabolites can be linked to insulin resistance, oxidative stress or a dysfunction of energy metabolism, suggesting that low birthweight in both twins and singletons are having an impact on these pathways in adulthood.

Journal article

Guerra S, Melén E, Sunyer J, Xu CJ, Lavi I, Benet M, Bustamante M, Carsin AE, Dobaño C, Guxens M, Tischer C, Vrijheid M, Kull I, Bergström A, Kumar A, Söderhäll C, Gehring U, Dijkstra DJ, van der Vlies P, Wickman M, Bousquet J, Postma DS, Anto JM, Koppelman GHet al., 2018, Genetic and epigenetic regulation of YKL-40 in childhood, Journal of Allergy and Clinical Immunology, Vol: 141, Pages: 1105-1114, ISSN: 0091-6749

© 2017 American Academy of Allergy, Asthma & Immunology Background: Circulating levels of the chitinase-like protein YKL-40 are influenced by genetic variation in its encoding gene (chitinase 3–like 1 [CHI3L1]) and are increased in patients with several diseases, including asthma. Epigenetic regulation of circulating YKL-40 early in life is unknown. Objective: We sought to determine (1) whether methylation levels at CHI3L1 CpG sites mediate the association of CHI3L1 single nucleotide polymorphisms (SNPs) with YKL-40 levels in the blood and (2) whether these biomarkers (CHI3L1 SNPs, methylation profiles, and YKL-40 levels) are associated with asthma in early childhood. Methods: We used data from up to 2405 participants from the Spanish Infancia y Medio Ambiente; the Swedish Barn/Children, Allergy, Milieu, Stockholm, Epidemiological survey; and the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohorts. Associations between 68 CHI3L1 SNPs, methylation levels at 14 CHI3L1 CpG sites in whole-blood DNA, and circulating YKL-40 levels at 4 years of age were tested by using correlation analysis, multivariable regression, and mediation analysis. Each of these biomarkers was also tested for association with asthma at 4 years of age by using multivariable logistic regression. Results: YKL-40 levels were significantly associated with 7 SNPs and with methylation at 5 CpG sites. Consistent associations between these 7 SNPs (particularly rs10399931 and rs4950928) and 5 CpG sites were observed. Alleles linked to lower YKL-40 levels were associated with higher methylation levels. Participants with high YKL-40 levels (defined as the highest YKL-40 tertile) had increased odds for asthma compared with subjects with low YKL-40 levels (meta-analyzed adjusted odds ratio, 1.90 [95% CI, 1.08-3.36]). In contrast, neither SNPs nor methylation levels at CpG sites in CHI3L1 were associated with asthma. Conclusions: The effects of CHI3L1 genetic variation on cir

Journal article

Matinolli H-M, Mannisto S, Sipola-Leppanen M, Tikanmaki M, Heinonen K, Eriksson JG, Wolke D, Lano A, Jarvelin M-R, Vaarasmaki M, Raikkonen K, Kajantie Eet al., 2018, Food and nutrient intakes in young adults born preterm, PEDIATRIC RESEARCH, Vol: 83, Pages: 589-596, ISSN: 0031-3998

BackgroundAdults born preterm have higher levels of cardiometabolic risk factors than their term-born peers. Studies have suggested that at least those born smallest eat less healthily. We examined the association between early (<34 weeks) and late (34–36 weeks) preterm birth and diet and food preferences in adult age.MethodsParticipants of two cohort studies located in Finland completed a validated food frequency questionnaire (FFQ) at the age of 24 years to assess their usual diet and the adherence to healthy eating guidelines by using a recommended diet index (RDI). Overall, 182 were born early preterm, 352 late preterm, and 631 were term-born controls.ResultsYoung women born early preterm scored 0.77 points (95% confidence interval (CI) 0.03, 1.51) lower in RDI when adjusted for sex, age, parental education, and early-life confounders, indicating a lower quality of diet. There were no differences between young women born late preterm and controls or among men. When food groups were assessed separately, men born early preterm had lower consumption of fruits and berries than controls.ConclusionsYoung women born early preterm have poorer adherence to the healthy eating guidelines than their peers born at term. Differences in diet may contribute to an increased cardiometabolic risk among adults born early preterm.

Journal article

Parra GR, Smith GL, Mason WA, Savolainen J, Chmelka MB, Miettunen J, Jarvelin M-R, Moilanen I, Veijola Jet al., 2018, Profiles of Contextual Risk at Birth and Adolescent Substance Use, JOURNAL OF CHILD AND FAMILY STUDIES, Vol: 27, Pages: 717-724, ISSN: 1062-1024

This study examined whether there are subgroups of families with distinct profiles of prenatal/birth contextual risk, and whether subgroup membership was differentially related to adolescent substance use. Data from the Northern Finland Birth Cohort 1986 were used. A five-class model provided the most meaningful solution. Large Family Size (7.72%) and Low Risk (69.69%) groups had the lowest levels of alcohol, cigarette, and illegal drug use. Similar high levels for each of the three substance-related outcomes were found for Parent Substance Misuse (11.20%), Maternal School Dropout (4.66%), and Socioeconomic Disadvantage (6.72%) groups. Maternal smoking and drinking while pregnant and paternal heavy alcohol use were found to be key prenatal risk factors that tended to cluster together and co-occur with other prenatal risk factors differently for different subgroups of youth.

Journal article

Beaumont RN, Warrington NM, Cavadino A, Tyrrell J, Nodzenski M, Horikoshi M, Geller F, Myhre R, Richmond RC, Paternoster L, Bradfield JP, Kreiner-Moller E, Huikari V, Metrustry S, Lunetta KL, Painter JN, Hottenga J-J, Allard C, Barton SJ, Espinosa A, Marsh JA, Potter C, Zhang G, Ang W, Berry DJ, Bouchard L, Das S, Hakonarson H, Heikkinen J, Helgeland O, Hocher B, Hofman A, Inskip HM, Jones SE, Kogevinas M, Lind PA, Marullo L, Medland SE, Murray A, Murray JC, Njolstad PR, Nohr EA, Reichetzeder C, Ring SM, Ruth KS, Santa-Marina L, Scholtens DM, Sebert S, Sengpiel V, Tuke MA, Vaudel M, Weedon MN, Willemsen G, Wood AR, Yaghootkar H, Muglia LJ, Bartels M, Relton CL, Pennell CE, Chatzi L, Estivill X, Holloway JW, Boomsma DI, Montgomery GW, Murabito JM, Spector TD, Power C, Jarvelin M-R, Bisgaard H, Grant SFA, Sorensen TIA, Jaddoe VW, Jacobsson B, Melbye M, McCarthy MI, Hattersley AT, Hayes MG, Frayling TM, Hivert M-F, Felix JF, Hypponen E, Lowe WL, Evans DM, Lawlor DA, Feenstra B, Freathy RMet al., 2018, Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics, Human Molecular Genetics, Vol: 27, Pages: 742-756, ISSN: 0964-6906

Genome-wide association studies of birth weight have focused on fetal genetics, whereas relatively little is known about the role of maternal genetic variation. We aimed to identify maternal genetic variants associated with birth weight that could highlight potentially relevant maternal determinants of fetal growth. We meta-analysed data on up to 8.7 million SNPs in up to 86 577 women of European descent from the Early Growth Genetics (EGG) Consortium and the UK Biobank. We used structural equation modelling (SEM) and analyses of mother–child pairs to quantify the separate maternal and fetal genetic effects. Maternal SNPs at 10 loci (MTNR1B, HMGA2, SH2B3, KCNAB1, L3MBTL3, GCK, EBF1, TCF7L2, ACTL9, CYP3A7) were associated with offspring birth weight at P < 5 × 10−8. In SEM analyses, at least 7 of the 10 associations were consistent with effects of the maternal genotype acting via the intrauterine environment, rather than via effects of shared alleles with the fetus. Variants, or correlated proxies, at many of the loci had been previously associated with adult traits, including fasting glucose (MTNR1B, GCK and TCF7L2) and sex hormone levels (CYP3A7), and one (EBF1) with gestational duration. The identified associations indicate that genetic effects on maternal glucose, cytochrome P450 activity and gestational duration, and potentially on maternal blood pressure and immune function, are relevant for fetal growth. Further characterization of these associations in mechanistic and causal analyses will enhance understanding of the potentially modifiable maternal determinants of fetal growth, with the goal of reducing the morbidity and mortality associated with low and high birth weights.

Journal article

Björkqvist J, Pesonen A-K, Kuula L, Matinolli H-M, Lano A, Sipola-Leppänen M, Tikanmäki M, Wolke D, Järvelin M-R, Eriksson JG, Andersson S, Vääräsmäki M, Heinonen K, Räikkönen K, Hovi P, Kajantie Eet al., 2018, Premature birth and circadian preference in young adulthood: evidence from two birth cohorts., Chronobiol Int, Pages: 1-10

A preference for eveningness (being a "night owl") and preterm birth (<37 weeks of gestation) are associated with similar adversities, such as elevated blood pressure, impaired glucose regulation, poorer physical fitness, and lower mood. Yet, it remains unclear if and how preterm birth is associated with circadian preference. The aim of this study was to assess this association across the whole gestation range, using both objective and subjective measurements of circadian preference. Circadian preference was measured among 594 young adults (mean age 24.3 years, SD 1.3) from two cohorts: the ESTER study and the Arvo Ylppö Longitudinal Study. We compared 83 participants born early preterm (<34 weeks) and 165 late preterm (34 to <37 weeks) with those born at term (≥37 weeks, n = 346). We also compared very low birth weight (VLBW, <1500 g) participants with term-born controls. We obtained objective sleep data with actigraphs that were worn for a mean period of 6.8 (SD 1.4) nights. Our primary outcome was sleep midpoint during weekdays and weekend. The sleep midpoint is the half-way time between falling asleep and waking up, and it represents sleep timing. We also investigated subjective chronotype with the Morningness-Eveningness Questionnaire (MEQ) in 688 (n = 138/221/329) ESTER participants. The MEQ consists of 19 questions, which estimates the respondent to be of a "morning", "evening," or "intermediate" chronotype, based on the Morningness-Eveningness Score (MES). We analyzed the data from the actigraphs and the MES with three linear regression models, and analyzed distribution of the chronotype class with Pearson χ2. There were no consistent differences across the study groups in sleep midpoint. As compared with those born at term, the mean differences in minutes:seconds and 95% confidence intervals for the sleep midpoint were: early preterm weekdays 11

Journal article

Jiang X, O'Reilly PF, Aschard H, Hsu Y-H, Richards JB, Dupuis J, Ingelsson E, Karasik D, Pilz S, Berry D, Kestenbaum B, Zheng J, Luan J, Sofianopoulou E, Streeten EA, Albanes D, Lutsey PL, Yao L, Tang W, Econs MJ, Wallaschofski H, Voelzke H, Zhou A, Power C, McCarthy MI, Michos ED, Boerwinkle E, Weinstein SJ, Freedman ND, Huang W-Y, Van Schoor NM, van der Velde N, de Groot LCPGM, Enneman A, Cupples LA, Booth SL, Vasan RS, Liu C-T, Zhou Y, Ripatti S, Ohlsson C, Vandenput L, Lorentzon M, Eriksson JG, Shea MK, Houston DK, Kritchevsky SB, Liu Y, Lohman KK, Ferrucci L, Peacock M, Gieger C, Beekman M, Slagboom E, Deelen J, van Heemst D, Kleber ME, Maerz W, de Boer IH, Wood AC, Rotter JI, Rich SS, Robinson-Cohen C, den Heijer M, Jarvelin M-R, Cavadino A, Joshi PK, Wilson JF, Hayward C, Lind L, Michaelsson K, Trompet S, Zillikens MC, Uitterlinden AG, Rivadeneira F, Broer L, Zgaga L, Campbell H, Theodoratou E, Farrington SM, Timofeeva M, Dunlop MG, Valdes AM, Tikkanen E, Lehtimaki T, Lyytikainen L-P, Kahonen M, Raitakari OT, Mikkila V, Ikram MA, Sattar N, Jukema JW, Wareham NJ, Langenberg C, Forouhi NG, Gundersen TE, Khaw K-T, Butterworth AS, Danesh J, Spector T, Wang TJ, Hypponen E, Kraft P, Kiel DPet al., 2018, Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels, Nature Communications, Vol: 9, Pages: 1-12, ISSN: 2041-1723

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10−9 at rs8018720 in SEC23A, and P = 1.9×10−14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene–gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

Journal article

Kroon MAGM, Akkerman-Nijland AM, Rottier BL, Koppelman GH, Akkerman OW, Touw DJet al., 2018, Drugs during pregnancy and breast feeding in women diagnosed with Cystic Fibrosis - An update, Journal of Cystic Fibrosis, Vol: 17, Pages: 17-25, ISSN: 1569-1993

Journal article

Liuhanen J, Suvisaari J, Kajantie E, Miettunen J, Sarin A-P, Jarvelin M-R, Lonnqvist J, Veijola J, Paunio Tet al., 2018, Interaction between compound genetic risk for schizophrenia and high birth weight contributes to social anhedonia and schizophrenia in women, PSYCHIATRY RESEARCH, Vol: 259, Pages: 148-153, ISSN: 0165-1781

Journal article

Demenais F, Margaritte-Jeannin P, Barnes KC, Cookson WOC, Altmüller J, Ang W, Barr RG, Beaty TH, Becker AB, Beilby J, Bisgaard H, Bjornsdottir US, Bleecker E, Bønnelykke K, Boomsma DI, Bouzigon E, Brightling CE, Brossard M, Brusselle GG, Burchard E, Burkart KM, Bush A, Chan-Yeung M, Chung KF, Couto Alves A, Curtin JA, Custovic A, Daley D, de Jongste JC, Del-Rio-Navarro BE, Donohue KM, Duijts L, Eng C, Eriksson JG, Farrall M, Fedorova Y, Feenstra B, Ferreira MA, Australian Asthma Genetics Consortium AAGC collaborators, Freidin MB, Gajdos Z, Gauderman J, Gehring U, Geller F, Genuneit J, Gharib SA, Gilliland F, Granell R, Graves PE, Gudbjartsson DF, Haahtela T, Heckbert SR, Heederik D, Heinrich J, Heliövaara M, Henderson J, Himes BE, Hirose H, Hirschhorn JN, Hofman A, Holt P, Hottenga J, Hudson TJ, Hui J, Imboden M, Ivanov V, Jaddoe VWV, James A, Janson C, Jarvelin M-R, Jarvis D, Jones G, Jonsdottir I, Jousilahti P, Kabesch M, Kähönen M, Kantor DB, Karunas AS, Khusnutdinova E, Koppelman GH, Kozyrskyj AL, Kreiner E, Kubo M, Kumar R, Kumar A, Kuokkanen M, Lahousse L, Laitinen T, Laprise C, Lathrop M, Lau S, Lee Y-A, Lehtimäki T, Letort S, Levin AM, Li G, Liang L, Loehr LR, London SJ, Loth DW, Manichaikul A, Marenholz I, Martinez FJ, Matheson MC, Mathias RA, Matsumoto K, Mbarek H, McArdle WL, Melbye M, Melén E, Meyers D, Michel S, Mohamdi H, Musk AW, Myers RA, Nieuwenhuis MAE, Noguchi E, O'Connor GT, Ogorodova LM, Palmer CD, Palotie A, Park JE, Pennell CE, Pershagen G, Polonikov A, Postma DS, Probst-Hensch N, Puzyrev VP, Raby BA, Raitakari OT, Ramasamy A, Rich SS, Robertson CF, Romieu I, Salam MT, Salomaa V, Schlünssen V, Scott R, Selivanova PA, Sigsgaard T, Simpson A, Siroux V, Smith LJ, Solodilova M, Standl M, Stefansson K, Strachan DP, Stricker BH, Takahashi A, Thompson PJ, Thorleifsson G, Thorsteinsdottir U, Tiesler CMT, Torgerson DG, Tsunoda T, Uitterlinden AG, van der Valk RJP, Vaysse A, Vedantam S, von Berg A, von Mutius E, Vonk JM, Waage J, Wareham NJ, Weiss STet al., 2017, Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks, Nature Genetics, Vol: 50, Pages: 42-53, ISSN: 1061-4036

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

Journal article

Kiviniemi AM, Perkiomaki N, Auvinen J, Niemela M, Tammelin T, Puukka K, Ruokonen A, Keinanen-Kiukaanniemi S, Tulppo MP, Jarvelin M-R, Jamsa T, Huikuri HV, Korpelainen Ret al., 2017, Fitness, Fatness, Physical Activity, and Autonomic Function in Midlife, MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, Vol: 49, Pages: 2459-2468, ISSN: 0195-9131

Journal article

Matinolli HM, Männistö S, Sipola-Leppänen M, Tikanmäki M, Heinonen K, Lahti J, Lahti M, Wehkalampi K, Järvelin MR, Andersson S, Lano A, Vartia T, Wolke D, Eriksson JG, Vääräsmäki M, Räikkönen K, Kajantie Eet al., 2017, Corrigendum to: Body image and eating behavior in young adults born preterm: Symptoms Related to EDs in Young Adults Born Preterm (International Journal of Eating Disorders, (2016), 49, 6, (572-580), 10.1002/eat.22553), International Journal of Eating Disorders, Vol: 50, Pages: 1442-1443, ISSN: 0276-3478

© 2017 Wiley Periodicals, Inc. In the publication listed above, errors were noted in the Figure 1. Flowchart of the study participants. In AYLS study the number of participants who were not traced during the invitation process is 280. The number of those who were invited to participate in a clinical examination was 1913 and the number of those who did not participate 777. In the box containing the numbers of participants whose length of gestation was confirmed from birth records, the numbers for the term-born control participants should be n=356 in Ester study and n=312 in AYLS study (Figure presented.) These errors do not affect any of the analyses or results of this study. The authors apologize for any inconvenience this may have caused.

Journal article

Ferreira MA, Vonk JM, Baurecht H, Marenholz I, Tian C, Hoffman JD, Helmer Q, Tillander A, Ullemar V, van Dongen J, Lu Y, Rüschendorf F, Esparza-Gordillo J, Medway CW, Mountjoy E, Burrows K, Hummel O, Grosche S, Brumpton BM, Witte JS, Hottenga J-J, Willemsen G, Zheng J, Rodríguez E, Hotze M, Franke A, Revez JA, Beesley J, Matheson MC, Dharmage SC, Bain LM, Fritsche LG, Gabrielsen ME, Balliu B, 23andMe Research Team, AAGC collaborators, BIOS consortium, LifeLines Cohort Study, Nielsen JB, Zhou W, Hveem K, Langhammer A, Holmen OL, Løset M, Abecasis GR, Willer CJ, Arnold A, Homuth G, Schmidt CO, Thompson PJ, Martin NG, Duffy DL, Novak N, Schulz H, Karrasch S, Gieger C, Strauch K, Melles RB, Hinds DA, Hübner N, Weidinger S, Magnusson PKE, Jansen R, Jorgenson E, Lee Y-A, Boomsma DI, Almqvist C, Karlsson R, Koppelman GH, Paternoster Let al., 2017, Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology., Nat Genet, Vol: 49, Pages: 1752-1757

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.

Journal article

Grgic O, Medina-Gomez C, Dhamo B, Trajanoska K, Vucic S, Ongkosuwito EM, Jaddoe VWV, Uitterlinden AG, Jarvelin M-R, Timpson N, Evans DM, Wolvius EB, Rivadeneira Fet al., 2017, Genome-Wide Association Study Identifies Three Novel Genetic Determinants of Dental Maturation., Annual Meeting of the American-Society-for-Bone-and-Mineral-Research (ASBMR), Publisher: WILEY, Pages: S132-S132, ISSN: 0884-0431

Conference paper

Rietschel L, Streit F, Zhu G, McAloney K, Frank J, Couvy-Duchesne B, Witt SH, Binz TM, Bolton JL, Hayward C, Direk N, Anderson A, Huffman J, Wilson JF, Campbell H, Rudan I, Wright A, Hastie N, Wild SH, Velders FP, Hofman A, Uitterlinden AG, Lahti J, Räikkönen K, Kajantie E, Widen E, Palotie A, Eriksson JG, Kaakinen M, Järvelin MR, Timpson NJ, Davey Smith G, Ring SM, Evans DM, St Pourcain B, Tanaka T, Milaneschi Y, Bandinelli S, Ferrucci L, Van Der Harst P, Rosmalen JG, Bakker SJ, Verweij N, Dullaart RP, Mahajan A, Lindgren CM, Morris A, Lind L, Ingelsson E, Anderson LN, Pennell CE, Lye SJ, Matthews SG, Eriksson J, Mellstrom D, Ohlsson C, Price JF, Strachan MW, Reynolds RM, Tiemeier H, Ripke S, Mattheisen M, Abdellaoui A, Adams MJ, Agerbo E, Air TM, Andlauer TF, Bacanu SA, Bækvad-Hansen M, Beekman AT, Bennett DA, Berger K, Bigdeli TB, Bybjerg-Grauholm Jet al., 2017, Hair cortisol in twins: heritability and genetic overlap with psychological variables and stress-system genes, Scientific Reports, Vol: 7, ISSN: 2045-2322

Hair cortisol concentration (HCC) is a promising measure of long-Term hypothalamus-pituitary-Adrenal (HPA) axis activity. Previous research has suggested an association between HCC and psychological variables, and initial studies of inter-individual variance in HCC have implicated genetic factors. However, whether HCC and psychological variables share genetic risk factors remains unclear. The aims of the present twin study were to: (i) assess the heritability of HCC; (ii) estimate the phenotypic and genetic correlation between HPA axis activity and the psychological variables perceived stress, depressive symptoms, and neuroticism; using formal genetic twin models and molecular genetic methods, i.e. polygenic risk scores (PRS). HCC was measured in 671 adolescents and young adults. These included 115 monozygotic and 183 dizygotic twin-pairs. For 432 subjects PRS scores for plasma cortisol, major depression, and neuroticism were calculated using data from large genome wide association studies. The twin model revealed a heritability for HCC of 72%. No significant phenotypic or genetic correlation was found between HCC and the three psychological variables of interest. PRS did not explain variance in HCC. The present data suggest that HCC is highly heritable. However, the data do not support a strong biological link between HCC and any of the investigated psychological variables.

Journal article

Gallo G, Vrijlandt EJLE, Arets HGM, Koppelman GH, Van der Zee DC, Hulscher JBF, Zwaveling Set al., 2017, Respiratory function after esophageal replacement in children., J Pediatr Surg, Vol: 52, Pages: 1736-1741

BACKGROUND: Children born with esophageal atresia require an anastomosis between the proximal and distal esophagus. When this distance is too wide (long gap esophageal atresia, LGEA) esophageal replacement strategies have to be deployed. The aim of this study was to assess long-term respiratory morbidity and lung function after esophageal replacement with either stomach (gastric pull-up, GPU) or jejunum (jejunal interposition, JI) for LGEA. METHODS: Retrospective cohort study. Patients operated with GPU and JI for LGEA (1985-2007) underwent a semi-structured interview and lung function testing (LFT). RESULTS: Seven GPU-patients and eight JI-patients were included. Median age was 12years. One patient per group could not perform LFT. Respiratory symptoms were reported by 13/15 patients (7/7 GPU-patients vs 6/8 JI-patients). All LFT items were lower than reference values; 6/13 patients showed restriction and 6/13 obstruction. All six GPU-patients had abnormal TLC and/or FEV1/FVC vs 3/7 after JI. Restriction was noted in 4/6 GPU-patients vs 2/7 JI-patients. CONCLUSION: After esophageal replacement for LGEA many children have impaired lung function and respiratory symptoms are common. Lung volumes seem decreased after GPU compared to JI. This may be caused by the intrathoracic stomach which may limit normal lung growth. Respiratory follow-up in adult life is important after esophageal replacement. LEVEL OF EVIDENCE: III.

Journal article

Liu DJ, Peloso GM, Yu H, Butterworth AS, Wang X, Mahajan A, Saleheen D, Emdin C, Alam D, Alves AC, Amouyel P, Di Angelantonio E, Arveiler D, Assimes TL, Auer PL, Baber U, Ballantyne CM, Bang LE, Benn M, Bis JC, Boehnke M, Boerwinkle E, Bork-Jensen J, Bottinger EP, Brandslund I, Brown M, Busonero F, Caulfield MJ, Chambers JC, Chasman DI, Chen YE, Chen Y-DI, Chowdhury R, Christensen C, Chu AY, Connell JM, Cucca F, Cupples LA, Damrauer SM, Davies G, Deary IJ, Dedoussis G, Denny JC, Dominiczak A, Dubé M-P, Ebeling T, Eiriksdottir G, Esko T, Farmaki A-E, Feitosa MF, Ferrario M, Ferrieres J, Ford I, Fornage M, Franks PW, Frayling TM, Frikke-Schmidt R, Fritsche LG, Frossard P, Fuster V, Ganesh SK, Gao W, Garcia ME, Gieger C, Giulianini F, Goodarzi MO, Grallert H, Grarup N, Groop L, Grove ML, Gudnason V, Hansen T, Harris TB, Hayward C, Hirschhorn JN, Holmen OL, Huffman J, Huo Y, Hveem K, Jabeen S, Jackson AU, Jakobsdottir J, Jarvelin M-R, Jensen GB, Jørgensen ME, Jukema JW, Justesen JM, Kamstrup PR, Kanoni S, Karpe F, Kee F, Khera AV, Klarin D, Koistinen HA, Kooner JS, Kooperberg C, Kuulasmaa K, Kuusisto J, Laakso M, Lakka T, Langenberg C, Langsted A, Launer LJ, Lauritzen T, Liewald DCM, Lin LA, Linneberg A, Loos RJF, Lu Y, Lu X, Mägi R, Malarstig A, Manichaikul A, Manning AK, Mäntyselkä P, Marouli E, Masca NGD, Maschio A, Meigs JB, Melander O, Metspalu A, Morris AP, Morrison AC, Mulas A, Müller-Nurasyid M, Munroe PB, Neville MJ, Nielsen JB, Nielsen SF, Nordestgaard BG, Ordovas JM, Mehran R, O'Donnell CJ, Orho-Melander M, Molony CM, Muntendam P, Padmanabhan S, Palmer CNA, Pasko D, Patel AP, Pedersen O, Perola M, Peters A, Pisinger C, Pistis G, Polasek O, Poulter N, Psaty BM, Rader DJ, Rasheed A, Rauramaa R, Reilly DF, Reiner AP, Renström F, Rich SS, Ridker PM, Rioux JD, Robertson NR, Roden DM, Rotter JI, Rudan I, Salomaa V, Samani NJ, Sanna S, Sattar N, Schmidt EM, Scott RA, Sever P, Sevilla RS, Shaffer CM, Sim X, Sivapalaratnam S, Small KS, Smith AV, Smith BH, Somayajula Set al., 2017, Exome-wide association study of plasma lipids in >300,000 individuals., Nature Genetics, Vol: 49, Pages: 1758-1766, ISSN: 1061-4036

We screened variants on an exome-focused genotyping array in >300,000 participants (replication in >280,000 participants) and identified 444 independent variants in 250 loci significantly associated with total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and/or triglycerides (TG). At two loci (JAK2 and A1CF), experimental analysis in mice showed lipid changes consistent with the human data. We also found that: (i) beta-thalassemia trait carriers displayed lower TC and were protected from coronary artery disease (CAD); (ii) excluding the CETP locus, there was not a predictable relationship between plasma HDL-C and risk for age-related macular degeneration; (iii) only some mechanisms of lowering LDL-C appeared to increase risk for type 2 diabetes (T2D); and (iv) TG-lowering alleles involved in hepatic production of TG-rich lipoproteins (TM6SF2 and PNPLA3) tracked with higher liver fat, higher risk for T2D, and lower risk for CAD, whereas TG-lowering alleles involved in peripheral lipolysis (LPL and ANGPTL4) had no effect on liver fat but decreased risks for both T2D and CAD.

Journal article

Maddock J, Zhou A, Cavadino A, Kuzma E, Bao Y, Smart MC, Saum K-U, Schoettker B, Engmann J, Kjaergaard M, Karhunen V, Zhan Y, Lehtimaki T, Rovio SP, Byberg L, Lahti J, Marques-Vidal P, Sen A, Perna L, Schirmer H, Singh-Manoux A, Auvinen J, Hutri-Kahonen N, Kahonen M, Kilander L, Raikkonen K, Melhus H, Ingelsson E, Guessous I, Petrovic KE, Schmidt H, Schmidt R, Vollenweider P, Lind L, Eriksson JG, Michaelsson K, Raitakari OT, Hagg S, Pedersen NL, Herzig K-H, Jarvelin M-R, Veijola J, Kivimaki M, Jorde R, Brenner H, Kumari M, Power C, Llewellyn DJ, Hypponen Eet al., 2017, Vitamin D and cognitive function: A Mendelian randomisation study, Scientific Reports, Vol: 7, ISSN: 2045-2322

The causal nature of the association between hypovitaminosis D and poor cognitive function in mid-tolater-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causalrelationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosento proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses werestratifed by 25(OH)D tertiles, sex and age. Random efects meta-analyses assessed associationsbetween 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memoryrelatedcognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D,pcurvature≤0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and thesynthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele.However, coefcients for associations with global or memory-related cognitive function were nonsignifcantand in opposing directions for DHCR7 and CYP2R1, with no overall association observedfor the synthesis score. Coefcients for the synthesis score and global and memory cognition weresimilar when stratifed by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)Dconcentration as a causal factor for cognitive performance in mid-to later life.

Journal article

Sharp GC, Salas LA, Monnereau C, Allard C, Yousefi P, Everson TM, Bohlin J, Xu Z, Huang R-C, Reese SE, Xu C-J, Baïz N, Hoyo C, Agha G, Roy R, Holloway JW, Ghantous A, Merid SK, Bakulski KM, Küpers LK, Zhang H, Richmond RC, Page CM, Duijts L, Lie RT, Melton PE, Vonk JM, Nohr EA, Williams-DeVane C, Huen K, Rifas-Shiman SL, Ruiz-Arenas C, Gonseth S, Rezwan FI, Herceg Z, Ekström S, Croen L, Falahi F, Perron P, Karagas MR, Quraishi BM, Suderman M, Magnus MC, Jaddoe VWV, Taylor JA, Anderson D, Zhao S, Smit HA, Josey MJ, Bradman A, Baccarelli AA, Bustamante M, Håberg SE, Pershagen G, Hertz-Picciotto I, Newschaffer C, Corpeleijn E, Bouchard L, Lawlor DA, Maguire RL, Barcellos LF, Davey Smith G, Eskenazi B, Karmaus W, Marsit CJ, Hivert M-F, Snieder H, Fallin MD, Melén E, Munthe-Kaas MC, Arshad H, Wiemels JL, Annesi-Maesano I, Vrijheid M, Oken E, Holland N, Murphy SK, Sørensen TIA, Koppelman GH, Newnham JP, Wilcox AJ, Nystad W, London SJ, Felix JF, Relton CLet al., 2017, Maternal BMI at the start of pregnancy and offspring epigenome-wide DNA methylation: findings from the pregnancy and childhood epigenetics (PACE) consortium, Human Molecular Genetics, Vol: 26, Pages: 4067-4085, ISSN: 0964-6906

Pre-pregnancy maternal obesity is associated with adverse offspring outcomes at birth and later in life. Individual studies have shown that epigenetic modifications such as DNA methylation could contribute. Within the Pregnancy and Childhood Epigenetics (PACE) Consortium, we meta-analysed the association between pre-pregnancy maternal BMI and methylation at over 450,000 sites in newborn blood DNA, across 19 cohorts (9,340 mother-newborn pairs). We attempted to infer causality by comparing the effects of maternal versus paternal BMI and incorporating genetic variation. In four additional cohorts (1,817 mother-child pairs), we meta-analysed the association between maternal BMI at the start of pregnancy and blood methylation in adolescents. In newborns, maternal BMI was associated with small (<0.2% per BMI unit (1 kg/m2), P < 1.06 × 10-7) methylation variation at 9,044 sites throughout the genome. Adjustment for estimated cell proportions greatly attenuated the number of significant CpGs to 104, including 86 sites common to the unadjusted model. At 72/86 sites, the direction of the association was the same in newborns and adolescents, suggesting persistence of signals. However, we found evidence for acausal intrauterine effect of maternal BMI on newborn methylation at just 8/86 sites. In conclusion, this well-powered analysis identified robust associations between maternal adiposity and variations in newborn blood DNA methylation, but these small effects may be better explained by genetic or lifestyle factors than a causal intrauterine mechanism. This highlights the need for large-scale collaborative approaches and the application of causal inference techniques in epigenetic epidemiology.

Journal article

Kraja AT, Evangelou E, Tzoulaki I, Zhang W, Gao H, Chambers J, Jarvelin MR, Kooner J, Poulter N, Sever P, Vergnaud AC, Elliott P, CHARGE EXOME BP, CHD Exome, Exome BP, GoT2DT2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Groupet al., 2017, New blood pressure associated loci identified in meta-analyses of 475,000 individuals, Circulation: Cardiovascular Genetics, Vol: 10, ISSN: 1942-325X

Background—Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results—Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10−8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions—We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.

Journal article

Schierding W, Antony J, Karhunen V, Vaarasmaki M, Franks S, Elliott P, Kajantie E, Sebert S, Blakemore A, Horsfield JA, Jarvelin MR, O'Sullivan J, Cutfield WSet al., 2017, GWAS on prolonged gestation (post-term birth): analysis of successive Finnish birth cohorts., Journal of Medical Genetics, Vol: 55, Pages: 55-63, ISSN: 1468-6244

Background Gestation is a crucial timepoint in human development. Deviation from a term gestational age correlates with both acute and long-term adverse health effects for the child. Both being born preterm and post-term, that is, having short and long gestational ages, are heritable and influenced by the prenatal and perinatal environment. Despite the obvious heritable component, specific genetic influences underlying differences in gestational age are poorly understood.Methods We investigated the genetic architecture of gestational age in 9141 individuals, including 1167 born post-term, across two Northern Finland cohorts born in 1966 or 1986.Results Here we identify one globally significant intronic genetic variant within the ADAMTS13 gene that is associated with prolonged gestation (p=4.85×10−8). Additional variants that reached suggestive levels of significance were identified within introns at the ARGHAP42 and TKT genes, and in the upstream (5’) intergenic regions of the B3GALT5 and SSBP2 genes. The variants near the ADAMTS13, B3GALT5, SSBP2 and TKT loci are linked to alterations in gene expression levels (cis-eQTLs). Luciferase assays confirmed the allele specific enhancer activity for the BGALT5 and TKT loci.Conclusions Our findings provide the first evidence of a specific genetic influence associated with prolonged gestation. This study forms a foundation for a better understanding of the genetic and long-term health risks faced by induced and post-term individuals. The long-term risks for induced individuals who have a previously overlooked post-term potential may be a major issue for current health providers.

Journal article

Benner C, Havulinna AS, Jarvelin M-R, Salomaa V, Ripatti S, Pirinen Met al., 2017, Prospects of Fine-Mapping Trait-Associated Genomic Regions by Using Summary Statistics from Genome-wide Association Studies, AMERICAN JOURNAL OF HUMAN GENETICS, Vol: 101, Pages: 539-551, ISSN: 0002-9297

Journal article

O'Reilly P, Socrates A, Euesden J, Jarvelin M-Ret al., 2017, CROSS-TRAIT POLYGENIC RISK SCORE SCAN REVEALS SHARED GENETIC AETIOLOGY ACROSS AN ARRAY OF PHENOTYPES, 23rd Annual World Congress of Psychiatric Genetics (WCPG), Publisher: ELSEVIER SCIENCE BV, Pages: S165-S165, ISSN: 0924-977X

Conference paper

Patwardhan I, Mason WA, Savolainen J, Chmelka MB, Miettunen J, Jarvelin M-Ret al., 2017, Childhood cumulative contextual risk and depression diagnosis among young adults: The mediating roles of adolescent alcohol use and perceived social support, JOURNAL OF ADOLESCENCE, Vol: 60, Pages: 16-26, ISSN: 0140-1971

Journal article

Tikanmaki M, Kaseva N, Tammelin T, Sipola-Leppanen M, Matinolli H-M, Eriksson JG, Jarvelin M-R, Vaarasmaki M, Kajantie Eet al., 2017, Leisure Time Physical Activity in Young Adults Born Preterm, JOURNAL OF PEDIATRICS, Vol: 189, Pages: 135-+, ISSN: 0022-3476

Journal article

Parra GR, Smith GL, Mason WA, Savolainen J, Chmelka MB, Miettunen J, Jarvelin M-Ret al., 2017, Tests of linear and nonlinear relations between cumulative contextual risk at birth and psychosocial problems during adolescence, JOURNAL OF ADOLESCENCE, Vol: 60, Pages: 64-73, ISSN: 0140-1971

Journal article

Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, Ntalla I, Surendran P, Liu C, Cook JP, Kraja AT, Drenos F, Loh M, Verweij N, Marten J, Karaman I, Lepe MPS, O'Reilly PF, Knight J, Snieder H, Kato N, He J, Tai ES, Said MA, Porteous D, Alver M, Poulter N, Farrall M, Gansevoort RT, Padmanabhan S, Magi R, Stanton A, Connell J, Bakker SJL, Metspalu A, Shields DC, Thom S, Brown M, Sever P, Esko T, Hayward C, van der Harst P, Saleheen D, Chowdhury R, Chambers JC, Chasman DI, Chakravarti A, Newton-Cheh C, Lindgren CM, Levy D, Kooner JS, Keavney B, Tomaszewski M, Samani NJ, Howson JMM, Tobin MD, Munroe PB, Ehret GB, Wain LV, Barnes MR, Tzoulaki I, Caulfield MJ, Elliott Pet al., 2017, Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk (vol 49, pg 403, 2017), NATURE GENETICS, Vol: 49, Pages: 1558-1558, ISSN: 1061-4036

Journal article

Lewis KM, Ruiz M, Goldblatt P, Morrison J, Porta D, Forastiere F, Hryhorczuk D, Zvinchuk O, Saurel-Cubizolles M-J, Lioret S, Annesi-Maesano I, Vrijheid M, Torrent M, Iniguez C, Larranaga I, Harskamp-van Ginkel MW, Vrijkotte TGM, Klanova J, Svancara J, Barross H, Correia S, Jarvelin M-R, Taanila A, Ludvigsson J, Faresjo T, Marmot M, Pikhart Het al., 2017, Mother's education and offspring asthma risk in 10 European cohort studies., European Journal of Epidemiology, Vol: 32, Pages: 797-805, ISSN: 0393-2990

Highly prevalent and typically beginning in childhood, asthma is a burdensome disease, yet the risk factors for this condition are not clarified. To enhance understanding, this study assessed the cohort-specific and pooled risk of maternal education on asthma in children aged 3-8 across 10 European countries. Data on 47,099 children were obtained from prospective birth cohort studies across 10 European countries. We calculated cohort-specific prevalence difference in asthma outcomes using the relative index of inequality (RII) and slope index of inequality (SII). Results from all countries were pooled using random-effects meta-analysis procedures to obtain mean RII and SII scores at the European level. Final models were adjusted for child sex, smoking during pregnancy, parity, mother's age and ethnicity. The higher the score the greater the magnitude of relative (RII, reference 1) and absolute (SII, reference 0) inequity. The pooled RII estimate for asthma risk across all cohorts was 1.46 (95% CI 1.26, 1.71) and the pooled SII estimate was 1.90 (95% CI 0.26, 3.54). Of the countries examined, France, the United Kingdom and the Netherlands had the highest prevalence's of childhood asthma and the largest inequity in asthma risk. Smaller inverse associations were noted for all other countries except Italy, which presented contradictory scores, but with small effect sizes. Tests for heterogeneity yielded significant results for SII scores. Overall, offspring of mothers with a low level of education had an increased relative and absolute risk of asthma compared to offspring of high-educated mothers.

Journal article

Felix JF, Joubert BR, Baccarelli AA, Sharp GC, Almqvist C, Annesi-Maesano I, Arshad H, Baïz N, Bakermans-Kranenburg MJ, Bakulski KM, Binder EB, Bouchard L, Breton CV, Brunekreef B, Brunst KJ, Burchard EG, Bustamante M, Chatzi L, Cheng Munthe-Kaas M, Corpeleijn E, Czamara D, Dabelea D, Davey Smith G, De Boever P, Duijts L, Dwyer T, Eng C, Eskenazi B, Everson TM, Falahi F, Fallin MD, Farchi S, Fernandez MF, Gao L, Gaunt TR, Ghantous A, Gillman MW, Gonseth S, Grote V, Gruzieva O, Håberg SE, Herceg Z, Hivert M-F, Holland N, Holloway JW, Hoyo C, Hu D, Huang R-C, Huen K, Järvelin M-R, Jima DD, Just AC, Karagas MR, Karlsson R, Karmaus W, Kechris KJ, Kere J, Kogevinas M, Koletzko B, Koppelman GH, Küpers LK, Ladd-Acosta C, Lahti J, Lambrechts N, Langie SAS, Lie RT, Liu AH, Magnus MC, Magnus P, Maguire RL, Marsit CJ, McArdle W, Melén E, Melton P, Murphy SK, Nawrot TS, Nisticò L, Nohr EA, Nordlund B, Nystad W, Oh SS, Oken E, Page CM, Perron P, Pershagen G, Pizzi C, Plusquin M, Raikkonen K, Reese SE, Reischl E, Richiardi L, Ring S, Roy RP, Rzehak P, Schoeters G, Schwartz DA, Sebert S, Snieder H, Sørensen TIA, Starling AP, Sunyer J, Taylor JA, Tiemeier H, Ullemar V, Vafeiadi M, Van Ijzendoorn MH, Vonk JM, Vriens A, Vrijheid M, Wang P, Wiemels JL, Wilcox AJ, Wright RJ, Xu C-J, Xu Z, Yang IV, Yousefi P, Zhang H, Zhang W, Zhao S, Agha G, Relton CL, Jaddoe VWV, London SJet al., 2017, Cohort profile: Pregnancy and Childhood Epigenetics (PACE) Consortium, International Journal of Epidemiology, Vol: 47, Pages: 22-23u, ISSN: 1464-3685

Journal article

Solomon SJ, Savolainen J, Mason WA, Miettunen J, January S-AA, Jarvelin M-Ret al., 2017, Does Educational Marginalization Mediate the Path from Childhood Cumulative Risk to Criminal Offending?, JOURNAL OF DEVELOPMENTAL AND LIFE-COURSE CRIMINOLOGY, Vol: 3, Pages: 326-346, ISSN: 2199-4641

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: limit=30&id=00169006&person=true&page=5&respub-action=search.html