Publications
165 results found
Pillas D, Hoggart CJ, Evans DM, et al., 2010, Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy, PLOS Genetics, Vol: 6, ISSN: 1553-7390
Tooth development is a highly heritable process which relates to other growth and developmental processes, and which interacts with the development of the entire craniofacial complex. Abnormalities of tooth development are common, with tooth agenesis being the most common developmental anomaly in humans. We performed a genome-wide association study of time to first tooth eruption and number of teeth at one year in 4,564 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966) and 1,518 individuals from the Avon Longitudinal Study of Parents and Children (ALSPAC). We identified 5 loci at P<5×10−8, and 5 with suggestive association (P<5×10−6). The loci included several genes with links to tooth and other organ development (KCNJ2, EDA, HOXB2, RAD51L1, IGF2BP1, HMGA2, MSRB3). Genes at four of the identified loci are implicated in the development of cancer. A variant within the HOXB gene cluster associated with occlusion defects requiring orthodontic treatment by age 31 years.
Dupuis J, Langenberg C, Prokopenko I, et al., 2010, New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk, Nature Genetics, Vol: 42, Pages: 105-U32, ISSN: 1546-1718
Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Rodriguez A, Kaakinen M, Moilanen I, et al., 2010, Mixed-Handedness Is Linked to Mental Health Problems in Children and Adolescents, PEDIATRICS, Vol: 125, Pages: E340-E348, ISSN: 0031-4005
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- Citations: 78
Koivukangas J, Tammelin T, Kaakinen M, et al., 2010, Physical activity and fitness in adolescents at risk for psychosis within the Northern Finland 1986 Birth Cohort, SCHIZOPHRENIA RESEARCH, Vol: 116, Pages: 152-158, ISSN: 0920-9964
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- Citations: 59
Pillas D, Hoggart CJ, Evans DM, et al., 2010, Correction: Genome-Wide Association Study Reveals Multiple Loci Associated with Primary Tooth Development during Infancy., PLoS Genet, Vol: 6, ISSN: 1553-7404
[This corrects the article on p. e1000856 in vol. 6.].
Bonnefond A, Vaxillaire M, Labrune Y, et al., 2009, Genetic variant m HK1 is associated with a proanemic state and A1C but not other glycemic control-related traits, Diabetes, Vol: 58, Pages: 2687-2697, ISSN: 0012-1797
OBJECTIVE A1C is widely considered the gold standard for monitoring effective blood glucose levels. Recently, a genome-wide association study reported an association between A1C and rs7072268 within HK1 (encoding hexokinase 1), which catalyzes the first step of glycolysis. HK1 deficiency in erythrocytes (red blood cells [RBCs]) causes severe nonspherocytic hemolytic anemia in both humans and mice.RESEARCH DESIGN AND METHODS The contribution of rs7072268 to A1C and the RBC-related traits was assessed in 6,953 nondiabetic European participants. We additionally analyzed the association with hematologic traits in 5,229 nondiabetic European individuals (in whom A1C was not measured) and 1,924 diabetic patients. Glucose control–related markers other than A1C were analyzed in 18,694 nondiabetic European individuals. A type 2 diabetes case-control study included 7,447 French diabetic patients.RESULTS Our study confirms a strong association between the rs7072268–T allele and increased A1C (β = 0.029%; P = 2.22 × 10−7). Surprisingly, despite adequate study power, rs7072268 showed no association with any other markers of glucose control (fasting- and 2-h post-OGTT–related parameters, n = 18,694). In contrast, rs7072268–T allele decreases hemoglobin levels (n = 13,416; β = −0.054 g/dl; P = 3.74 × 10−6) and hematocrit (n = 11,492; β = −0.13%; P = 2.26 × 10−4), suggesting a proanemic effect. The T allele also increases risk for anemia (836 cases; odds ratio 1.13; P = 0.018).CONCLUSIONS HK1 variation, although strongly associated with A1C, does not seem to be involved in blood glucose control. Since HK1 rs7072268 is associated with reduced hemoglobin levels and favors anemia, we propose that HK1 may influence A1C levels through its anemic effect or its effect on glucose metabolism in RBCs. These findings may have implications for type 2 diabetes diagnosis and clinical management because anemia i
Sovio U, Timpson NJ, Warrington NM, et al., 2009, ASSOCIATION BETWEEN FTO POLYMORPHISM, ADIPOSITY PEAK AND ADIPOSITY REBOUND IN THE NORTHERN FINLAND BIRTH COHORT 1966, Autumn Meeting of the British-Atherosclerosis-Society, Publisher: ELSEVIER IRELAND LTD, Pages: E4-E5, ISSN: 0021-9150
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- Citations: 2
Heid IM, Huth C, Loos RJF, et al., 2009, Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?, PLOS Genetics, Vol: 5, ISSN: 1553-7390
The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I2 measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I2 measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI≥32.5, 35.0, 37.5, 40.0 kg/m2 versus BMI<25 kg/m2) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study des
Rodriguez A, Olsen J, Kotimaa AJ, et al., 2009, Is prenatal alcohol exposure related to inattention and hyperactivity symptoms in children? Disentangling the effects of social adversity, JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY, Vol: 50, Pages: 1073-1083, ISSN: 0021-9630
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- Citations: 41
Sovio U, Bennett AJ, Millwood IY, et al., 2009, Genetic Determinants of Height Growth Assessed Longitudinally from Infancy to Adulthood in the Northern Finland Birth Cohort 1966, PLOS Genetics, Vol: 5, ISSN: 1553-7390
Recent genome-wide association (GWA) studies have identified dozens of common variants associated with adult height. However, it is unknown how these variants influence height growth during childhood. We derived peak height velocity in infancy (PHV1) and puberty (PHV2) and timing of pubertal height growth spurt from parametric growth curves fitted to longitudinal height growth data to test their association with known height variants. The study consisted of N = 3,538 singletons from the prospective Northern Finland Birth Cohort 1966 with genotype data and frequent height measurements (on average 20 measurements per person) from 0–20 years. Twenty-six of the 48 variants tested associated with adult height (p<0.05, adjusted for sex and principal components) in this sample, all in the same direction as in previous GWA scans. Seven SNPs in or near the genes HHIP, DLEU7, UQCC, SF3B4/SV2A, LCORL, and HIST1H1D associated with PHV1 and five SNPs in or near SOCS2, SF3B4/SV2A, C17orf67, CABLES1, and DOT1L with PHV2 (p<0.05). We formally tested variants for interaction with age (infancy versus puberty) and found biologically meaningful evidence for an age-dependent effect for the SNP in SOCS2 (p = 0.0030) and for the SNP in HHIP (p = 0.045). We did not have similar prior evidence for the association between height variants and timing of pubertal height growth spurt as we had for PHVs, and none of the associations were statistically significant after correction for multiple testing. The fact that in this sample, less than half of the variants associated with adult height had a measurable effect on PHV1 or PHV2 is likely to reflect limited power to detect these associations in this dataset. Our study is the first genetic association analysis on longitudinal height growth in a prospective cohort from birth to adulthood and gives grounding for future research on the genetic regulation of human height during different periods of growth.
Sabatti C, Service SK, Hartikainen A-L, et al., 2009, Genome-wide association analysis of metabolic traits in a birth cohort from a founder population, NATURE GENETICS, Vol: 41, Pages: 35-46, ISSN: 1061-4036
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- Citations: 575
Prokopenko I, Langenberg C, Florez JC, et al., 2009, Variants in <i>MTNR1B</i> influence fasting glucose levels, NATURE GENETICS, Vol: 41, Pages: 77-81, ISSN: 1061-4036
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- Citations: 573
Prokopenko I, Aulchenko Y, Kaakinen M, et al., 2008, Meta-analysis of genome-wide association data involving 6,100 adults of European origin identifies common variants associated with fasting glucose levels, DIABETOLOGIA, Vol: 51, Pages: S11-S11, ISSN: 0012-186X
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- Citations: 1
Kaakinen M, Prokopenko I, Rayner WN, et al., 2008, Genome-wide association (GWA) analysis in 4000 members of a Finnish birth cohort identifies common variants associated with fasting insulin levels and related metabolic traits, DIABETOLOGIA, Vol: 51, Pages: S11-S11, ISSN: 0012-186X
Smalley SL, McGough JJ, Moilanen IK, et al., 2007, Prevalence and psychiatric comorbidity of attention-deficit/hyperactivity disorder in an adolescent Finnish population, JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY, Vol: 46, Pages: 1575-1583, ISSN: 0890-8567
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- Citations: 126
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