Leena Peltonen

University of Helsinki, Helsinki, Uusimaa, Finland

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Publications (851)7868.93 Total impact

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    ABSTRACT: This study reports the potential of different polymers and polymer incorporation methods to inhibit crystallisation and maintain supersaturation of amorphous indomethacin (IND) in aqueous suspensions during storage. Three different polymers (poly(vinyl pyrrolidone) (PVP), hydroxypropyl methyl cellulose (HPMC) and Soluplus® (SP)) were used and included in the suspensions either as a solid dispersion (SD) with IND or dissolved in the suspension medium prior to the addition of amorphous IND. The total concentrations of both IND and the polymer in the suspensions were kept the same for both methods of polymer incorporation. All the polymers (with both incorporation methods) inhibited crystallisation of the amorphous IND. The SDs were better than the predissolved polymer solutions at inhibiting crystallisation. The SDs were also better at maintaining drug supersaturation. SP showed a higher IND crystallisation inhibition and supersaturation potential than the other polymers. However, this depended on the method of addition. IND in SD with SP did not crystallise, nor did the SD generate any drug supersaturation, whereas IND in the corresponding predissolved SP solution crystallised (into the recently characterised η polymorphic form of the drug) but also led to a more than 20-fold higher IND solution concentration than that observed for crystalline IND. The ranking of the polymers with respect to crystallisation inhibition potential in SDs was SP≫PVP>HPMC. Overall, this study showed that both polymer type and polymer incorporation method strongly impact amorphous form stability and drug supersaturation in aqueous suspensions. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmaceutics and biopharmaceutics: official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V 06/2015; DOI:10.1016/j.ejpb.2015.06.005 · 4.25 Impact Factor
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    Molecular Psychiatry 02/2015; 20(2):207-214. DOI:10.1038/mp.2013.195 · 15.15 Impact Factor
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    ABSTRACT: Neuronal ceroid lipofuscinosis (NCL) diseases consist of a group of genetically inherited neurodegenerative disorders that share common symptoms such as seizures, psychomotor retardation, blindness, and premature death. Although gene defects behind the NCL diseases are well characterized, very little is known how these defects affect normal development of the brain and cause the pathology of the disease. To obtain understanding of the development of the cell types that are mostly affected by defective function of CLN proteins, timing of expression of CLN2, CLN3 and CLN5 genes was investigated in developing mouse brain. The relationship between the expression pattern and the developmental stage of the brain showed that these genes are co-expressed spatially and temporally during brain development. Throughout the development strong expression of the three mRNAs was detected in germinal epithelium and in ventricle regions, hippocampus and cerebellum, all representing regions that are known to be associated with the formation of new neurons. More specifically, RT-PCR studies on developing mouse cortices revealed that the CLN genes were temporally co-expressed in the neural progenitor cells together with known stem cell markers. This suggested that CLN2, CLN3 and CLN5 genes may play an important role in early embryonal neurogenesis.
    Experimental and Molecular Pathology 10/2014; 97(3). DOI:10.1016/j.yexmp.2014.10.003 · 2.88 Impact Factor
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    ABSTRACT: IMPORTANCE We investigated the variation in neuropsychological function explained by risk alleles at the psychosis susceptibility gene ZNF804A and its interacting partners using single nucleotide polymorphisms (SNPs), polygenic scores, and epistatic analyses. Of particular importance was the relative contribution of the polygenic score vs epistasis in variation explained. OBJECTIVES To (1) assess the association between SNPs in ZNF804A and the ZNF804A polygenic score with measures of cognition in cases with psychosis and (2) assess whether epistasis within the ZNF804A pathway could explain additional variation above and beyond that explained by the polygenic score. DESIGN, SETTING, AND PARTICIPANTS Patients with psychosis (n = 424) were assessed in areas of cognitive ability impaired in schizophrenia including IQ, memory, attention, and social cognition. We used the Psychiatric GWAS Consortium 1 schizophrenia genome-wide association study to calculate a polygenic score based on identified risk variants within this genetic pathway. Cognitive measures significantly associated with the polygenic score were tested for an epistatic component using a training set (n = 170), which was used to develop linear regression models containing the polygenic score and 2-SNP interactions. The best-fitting models were tested for replication in 2 independent test sets of cases: (1) 170 individuals with schizophrenia or schizoaffective disorder and (2) 84 patients with broad psychosis (including bipolar disorder, major depressive disorder, and other psychosis). MAIN OUTCOMES AND MEASURES Participants completed a neuropsychological assessment battery designed to target the cognitive deficits of schizophrenia including general cognitive function, episodic memory, working memory, attentional control, and social cognition. RESULTS Higher polygenic scores were associated with poorer performance among patients on IQ, memory, and social cognition, explaining 1% to 3% of variation on these scores (range, P = .01 to .03). Using a narrow psychosis training set and independent test sets of narrow phenotype psychosis (schizophrenia and schizoaffective disorder), broad psychosis, and control participants (n = 89), the addition of 2 interaction terms containing 2 SNPs each increased the R2 for spatial working memory strategy in the independent psychosis test sets from 1.2% using the polygenic score only to 4.8% (P = .11 and .001, respectively) but did not explain additional variation in control participants. CONCLUSIONS AND RELEVANCE These data support a role for the ZNF804A pathway in IQ, memory, and social cognition in cases. Furthermore, we showed that epistasis increases the variation explained above the contribution of the polygenic score.
    JAMA Psychiatry 05/2014; DOI:10.1001/jamapsychiatry.2014.528 · 12.01 Impact Factor
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    ABSTRACT: To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
    Nature Genetics 03/2014; 46(3):234-244. DOI:10.1038/ng.2897 · 29.65 Impact Factor
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    ABSTRACT: The Wellcome Trust Case Control Consortium 3 anorexia nervosa genome-wide association scan includes 2907 cases from 15 different populations of European origin genotyped on the Illumina 670K chip. We compared methods for identifying population stratification, and suggest list of markers that may help to counter this problem. It is usual to identify population structure in such studies using only common variants with minor allele frequency (MAF) >5%; we find that this may result in highly informative SNPs being discarded, and suggest that instead all SNPs with MAF >1% may be used. We established informative axes of variation identified via principal component analysis and highlight important features of the genetic structure of diverse European-descent populations, some studied for the first time at this scale. Finally, we investigated the substructure within each of these 15 populations and identified SNPs that help capture hidden stratification. This work can provide information regarding the designing and interpretation of association results in the International Consortia
    European Journal of HumanGenetics 02/2014; 22(10). DOI:10.1038/ejhg.2014.1. · 4.23 Impact Factor
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    ABSTRACT: Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge–purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10−7) in SOX2OT and rs17030795 (P=5.84 × 10−6) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10−6) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10−6) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10−6), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.
    Molecular Psychiatry 02/2014; DOI:10.1038/mp.2013.187 · 15.15 Impact Factor
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    ABSTRACT: This study reports the appearance and characterization of multiple new polymorphic forms of indomethacin (IND). Considering the interest in amorphous suspensions for toxicology studies of poorly water soluble drugs, we sought to investigate the crystallization behaviour of amorphous IND in aqueous suspension. Specifically, the effect of pH and temperature on crystallization behaviour was studied. Quench cooled amorphous powder was added to buffered media at different pH values (1.2, 4.5, and 6.8) at 5 and 25°C. Both the solid and solution were analyzed at different time points up to 24 h. ATR-FTIR-spectroscopy (with principal component analysis) was used to study solid-phase transformations and UV-spectroscopy used to probe solution concentration. The crystallization onset time decreased and rate of crystallization increased with increasing pH and temperature. Diverse polymorphic forms were observed, with three new forms being identified; these were named ε, ζ and η. At 25°C, the amorphous form recrystallized directly to the α form, except at pH 6.8, where it initially converted briefly into the ε form. At 5°C, all three new polymorphic forms were observed sequentially in the order ε, ζ and then η, with the number of these forms observed increasing sequentially with decreasing pH. The three new forms exhibited distinct XPRD, DSC, and FTIR and Raman spectroscopy profiles. The solution concentration profiles suggest that the relative physical stabilities of the polymorphs at 5°C from lowest to highest is ε < ζ < η < α. The appearance of new polymorphs in this study, suggests that amorphous suspensions are worth considering when performing polymorphic screening studies.
    Molecular Pharmaceutics 09/2013; 10(12). DOI:10.1021/mp400299a · 4.79 Impact Factor
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    ABSTRACT: Recent genome-wide association studies have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms in several Finnish cohorts, with up to 32 669 individuals after exclusion of prevalent CVD cases. The median follow-up was 9.8 years, during which 2295 incident CVD events occurred. We created GRSs separately for systolic BP and diastolic BP by multiplying the risk allele count of each single nucleotide polymorphism by the effect size estimated in published genome-wide association studies. We performed Cox regression analyses with and without adjustment for clinical factors, including BP at baseline in each cohort. The results were combined by inverse variance-weighted fixed-effects meta-analysis. The GRSs were strongly associated with systolic BP and diastolic BP, and baseline hypertension (all P<10(-62)). Hazard ratios comparing the highest quintiles of systolic BP and diastolic BP GRSs with the lowest quintiles after adjustment for age, age squared, and sex were 1.25 (1.07-1.46; P=0.006) and 1.23 (1.05-1.43; P=0.01), respectively, for incident coronary heart disease; 1.24 (1.01-1.53; P=0.04) and 1.35 (1.09-1.66; P=0.005), respectively, for incident stroke; and 1.23 (1.08-1.40; P=2×10(-6)) and 1.26 (1.11-1.44; P=5×10(-4)), respectively, for composite CVD. In conclusion, BP findings from genome-wide association studies are strongly replicated. GRSs comprising bona fide BP-single nucleotide polymorphisms predicted CVD risk, consistent with a lifelong effect on BP of these variants collectively.
    Hypertension 03/2013; 61(5). DOI:10.1161/HYPERTENSIONAHA.111.00649 · 7.63 Impact Factor
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    ABSTRACT: OBJECTIVE: Low high-density lipoprotein cholesterol (HDL-C) is associated with cardiometabolic pathologies. In this study, we investigate the biological pathways and individual genes behind low HDL-C by integrating results from 3 high-throughput data sources: adipose tissue transcriptomics, HDL lipidomics, and dense marker genotypes from Finnish individuals with low or high HDL-C (n=450).Approach and Results-In the pathway analysis of genetic data, we demonstrate that genetic variants within inflammatory pathways were enriched among low HDL-C associated single-nucleotide polymorphisms, and the expression of these pathways upregulated in the adipose tissue of low HDL-C subjects. The lipidomic analysis highlighted the change in HDL particle quality toward putatively more inflammatory and less vasoprotective state in subjects with low HDL-C, as evidenced by their decreased antioxidative plasmalogen contents. We show that the focal point of these inflammatory pathways seems to be the human leukocyte antigen region with its low HDL-associated alleles also associating with more abundant local transcript levels in adipose tissue, increased plasma vascular cell adhesion molecule 1 levels, and decreased HDL particle plasmalogen contents, markers of adipose tissue inflammation, vascular inflammation, and HDL antioxidative potential, respectively. In a population-based look-up of the inflammatory pathway single-nucleotide polymorphisms in a large Finnish cohorts (n=11&emsp14;211), no association of the human leukocyte antigen region was detected for HDL-C as quantitative trait, but with extreme HDL-C phenotypes, implying the presence of low or high HDL genes in addition to the population-genomewide association studies-identified HDL genes. CONCLUSIONS: Our study highlights the role of inflammation with a genetic component in subjects with low HDL-C and identifies novel cis-expression quantitative trait loci variants in human leukocyte antigen region to be associated with low HDL-C.
    Arteriosclerosis Thrombosis and Vascular Biology 02/2013; 33(4). DOI:10.1161/ATVBAHA.112.300733 · 5.53 Impact Factor
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    ABSTRACT: To identify susceptibility loci for visceral leishmaniasis, we undertook genome-wide association studies in two populations: 989 cases and 1,089 controls from India and 357 cases in 308 Brazilian families (1,970 individuals). The HLA-DRB1-HLA-DQA1 locus was the only region to show strong evidence of association in both populations. Replication at this region was undertaken in a second Indian population comprising 941 cases and 990 controls, and combined analysis across the three cohorts for rs9271858 at this locus showed P(combined) = 2.76 × 10(-17) and odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.30-1.52. A conditional analysis provided evidence for multiple associations within the HLA-DRB1-HLA-DQA1 region, and a model in which risk differed between three groups of haplotypes better explained the signal and was significant in the Indian discovery and replication cohorts. In conclusion, the HLA-DRB1-HLA-DQA1 HLA class II region contributes to visceral leishmaniasis susceptibility in India and Brazil, suggesting shared genetic risk factors for visceral leishmaniasis that cross the epidemiological divides of geography and parasite species.
    Nature Genetics 01/2013; DOI:10.1038/ng.2518 · 29.65 Impact Factor
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    ABSTRACT: To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.
    Nature Genetics 11/2012; DOI:10.1038/ng.2467 · 29.65 Impact Factor
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    ABSTRACT: By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.
    Nature 11/2012; 491(7422-7422):56-65. DOI:10.1038/nature11632 · 42.35 Impact Factor
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    ABSTRACT: Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene-environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors (P = 3.98 × 10-8). We followed up the association in further genotyped monozygotic twins (N = 1,261), which showed a moderate association for the variant (P = 0.200, same direction of an effect). In addition, we report a new association on the level of apolipoprotein A-II (P = 4.03 × 10-8).
    Twin Research and Human Genetics 10/2012; 15(6):1-9. DOI:10.1017/thg.2012.63 · 1.92 Impact Factor
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    ABSTRACT: Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P(combined) = 4.09 × 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P(combined) = 2.74 × 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.
    Nature Genetics 09/2012; 44(10):1131-1136. DOI:10.1038/ng.2408 · 29.65 Impact Factor
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    ABSTRACT: Barrett's esophagus is an increasingly common disease that  is strongly associated with reflux of stomach acid and usually  a hiatus hernia, and it strongly predisposes to esophageal  adenocarcinoma (EAC), a tumor with a very poor prognosis.  We report the first genome-wide association study on Barrett's  esophagus, comprising ,852 UK cases and 5,72 UK controls  in the discovery stage and 5,986 cases and 2,825 controls in  the replication stage. Variants at two loci were associated with  disease risk: chromosome 6p2, rs9257809 (P combined  =   4.09 × 0 −9 ; odds ratio (OR) = .2, 95% confidence interval  (CI) =.3–.28), within the major histocompatibility complex  locus, and chromosome 6q24, rs9936833 (P combined  =   2.74 × 0 −0 ; OR = .4, 95% CI = .0–.9), for which the  closest protein-coding gene is FOXF1, which is implicated in  esophageal development and structure. We found evidence that  many common variants of small effect contribute to genetic  susceptibility to Barrett's esophagus and that SNP alleles  predisposing to obesity also increase risk for Barrett's esophagus. Barrett's esophagus is one of the most common premalignant lesions in the western world. It affects over 2% of the adult population and, unlike bowel polyps, lacks any proven effective therapy 1 . In the major-ity of cases, Barrett's esophagus is associated with chronic gastro-esophageal reflux disease (GERD), including esophagitis 2,3 . Over 80% of affected individuals have a hiatus hernia in the lower esophagus that facilitates the reflux of acid and bile into the esophagus 4 . The measured annual risk of EAC in individuals with Barrett's esophagus varies widely but is approximately 0.4–1% (refs. 5–7). Notably, the incidence of EAC has been rising by 3% each year for the last 30 years; it is now the fifth most common cancer in the UK 8 . Despite modern multimodality therapy, the prog-nosis for EAC remains poor, with a 9–15% 5-year survival rate 9,10 . The etiology of Barrett's esophagus is not well characterized. Environmental factors, such as diet, are weakly associated with GERD, Barrett's esophagus and EAC, and obesity is a known risk factor for all three conditions 11 . There is also evidence implicating genetic factors: relative risks are increased by 2-to 4-fold for GERD, Barrett's esophagus and EAC when one first-degree relative is affected 12–17 . A segregation analysis of 881 pedigrees of familial Barrett's esophagus supports an incompletely dominant inheritance model with a polygenic component 18 . Extensive candidate gene and linkage searches have to date been unsuccessful in identifying genetic variants that are associated with risk of Barrett's esophagus 19 . As part of the Wellcome Trust Case Control Consortium 2 (WTCCC2) study of 15 common disorders and traits, we present the results of the first genome-wide association study of Barrett's esophagus susceptibility. Using a discovery cohort from the UK (with case samples from the Aspirin and Esomeprazole Chemoprevention Trial of Cancer in Barrett's esophagus (AspECT)) 20 and five repli-cation cohorts (including case samples from CHemoprevention Of Premalignant Intestinal Neoplasia (ChOPIN) and Esophageal Adenocarcinoma GenEtics Consortium (EAGLE) studies 9,20), we identified two variants associated with Barrett's esophagus, each with combined evidence at P < 5 × 10 −8 . The analysis workflow is outlined in Supplementary Figure 1, and characteristics of the case and con-trol samples that were included can be found in the Online Methods and Supplementary Table 1. For the discovery analysis, cases with histologically confirmed Barrett's esophagus (Online Methods) were recruited from sites across the UK (Supplementary Table 2). Population controls were taken from the WTCCC2 common set of 1958 Birth Cohort (58C) and National Blood Service (UKBS) samples as previously described 21 .
    Nature Genetics 09/2012; · 29.65 Impact Factor
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    ABSTRACT: To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
    Nature Genetics 08/2012; 44(9):981-90. DOI:10.1038/ng.2383 · 29.65 Impact Factor

Publication Stats

60k Citations
7,868.93 Total Impact Points


  • 1986–2015
    • University of Helsinki
      • • Faculty of Pharmacy
      • • Institute for Molecular Medicine Finland (FIMM)
      • • Department of Medical Genetics
      • • Department of Psychiatry
      • • Department of Dental Public Health
      • • Institute of Biomedicine
      • • Department of Neurology
      • • Department of Oral Medicine
      • • Department of Clinical Chemistry
      • • Transplantation Laboratory
      • • Department of Ophthalmology
      • • Recombinant DNA Laboratory
      Helsinki, Uusimaa, Finland
  • 1999–2014
    • University of California, Los Angeles
      • • Department of Human Genetics
      • • Department of Statistics
      • • Department of Medicine
      Los Ángeles, California, United States
    • Oregon Health and Science University
      • Department of Biochemistry & Molecular Biology
      Portland, Oregon, United States
  • 2012
    • McGill University
      • Department of Epidemiology, Biostatistics and Occupational Health
      Montréal, Quebec, Canada
  • 2008–2012
    • Wellcome Trust Sanger Institute
      Cambridge, England, United Kingdom
    • Oulu University Hospital
      Uleoborg, Northern Ostrobothnia, Finland
  • 2003–2012
    • Institute for Molecular Medicine, Finland
      Helsinki, Southern Finland Province, Finland
  • 2009–2011
    • National Institute for Health and Welfare, Finland
      • Public Health Genomics Unit
      Helsinki, Uusimaa, Finland
  • 1982–2011
    • University of Oulu
      • • Department of Medical Biochemistry and Molecular Biology
      • • Institute of Health Sciences
      • • Biocenter Oulu
      • • Department of Biochemistry
      • • Department of Ophthalmology
      • • Institute of Biomedicine
      • • Department of Dermatology and Venereology
      Uleoborg, Northern Ostrobothnia, Finland
  • 2010
    • University of Exeter
      • Peninsula College of Medicine and Dentistry
      Exeter, ENG, United Kingdom
  • 1988–2010
    • National Public Health Institute
      Helsinki, Southern Finland Province, Finland
  • 2004–2009
    • Broad Institute of MIT and Harvard
      • Program in Medical and Population Genetics
      Cambridge, Massachusetts, United States
  • 1995–2009
    • Helsinki University Central Hospital
      • • Department of Clinical Chemistry
      • • Laboratory of Molecular Genetics
      • • Department of Medicine
      Helsinki, Southern Finland Province, Finland
    • The University of Manchester
      Manchester, England, United Kingdom
  • 1994–2008
    • Lund University
      • • Competence Centre for Clinical Research
      • • Department of Rheumatology
      Lund, Skåne, Sweden
    • Biocenter Finland
      Helsinki, Southern Finland Province, Finland
  • 2000–2004
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      Torrance, California, United States
  • 2002
    • CSU Mentor
      Long Beach, California, United States
    • Academy of Finland
      Helsinki, Southern Finland Province, Finland
  • 2001
    • University of Jyväskylä
      • Department of Health Sciences
      Jyväskylä, Western Finland, Finland
    • Johns Hopkins Medicine
      Baltimore, Maryland, United States
    • Beckman Research Institute
      Дуарте, California, United States
  • 1998
    • Howard Hughes Medical Institute
      Ashburn, Virginia, United States
  • 1997
    • University of Kuopio
      Kuopio, Northern Savo, Finland
    • Max Planck Institute for Molecular Genetics
      Berlín, Berlin, Germany
  • 1996
    • University of Joensuu
      • Department of Chemistry
      Yoensu, Eastern Finland Province, Finland
  • 1992–1996
    • University of Turku
      Turku, Province of Western Finland, Finland
    • Thomas Jefferson University
      Philadelphia, Pennsylvania, United States
  • 1990
    • Kuopio University Hospital
      • Department of Clinical Genetics
      Kuopio, Province of Eastern Finland, Finland
  • 1984
    • The John F. Kennedy Institute, Denmark
      Glostrup, Capital Region, Denmark