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- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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| 2. |
- Ikram, M. Arfan, et al.
(författare)
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Common variants at 6q22 and 17q21 are associated with intracranial volume
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
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| 3. |
- Taal, H. Rob, et al.
(författare)
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Common variants at 12q15 and 12q24 are associated with infant head circumference
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:5, s. 532-538
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Tidskriftsartikel (refereegranskat)abstract
- To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
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| 4. |
- Yang, J, et al.
(författare)
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Prevalence of obesity was related to HLA-DQ in 2-4-year-old children at genetic risk for type 1 diabetes.
- 2014
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 1476-5497 .- 0307-0565. ; 38:12, s. 1491-1496
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:Body size is postulated to modulate type 1 diabetes as either a trigger of islet autoimmunity or an accelerator to clinical onset after seroconversion. As overweight and obesity continue to rise among children, the aim of this study was to determine whether human leukocyte antigen DQ (HLA-DQ) genotypes may be related to body size among children genetically at risk for type 1 diabetes.Methods:Repeated measures of weight and height were collected from 5969 children 2-4 years of age enrolled in The Environmental Determinants of Diabetes in the Young prospective study. Overweight and obesity was determined by the International Obesity Task Force cutoff values that correspond to body mass index (BMI) of 25 and 30 kg m(-)(2) at age 18.Results:The average BMI was comparable across specific HLA genotypes at every age point. The proportion of overweight was not different by HLA, but percent obesity varied by age with a decreasing trend among DQ2/8 carriers (P for trend=0.0315). A multivariable regression model suggested DQ2/2 was associated with higher obesity risk at age 4 (odds ratio, 2.41; 95% confidence interval, 1.21-4.80) after adjusting for the development of islet autoantibody and/or type 1 diabetes.Conclusions:The HLA-DQ2/2 genotype may predispose to obesity among 2-4-year-old children with genetic risk for type 1 diabetes.International Journal of Obesity advance online publication, 29 April 2014; doi:10.1038/ijo.2014.55.
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| 7. |
- Lee, H-S, et al.
(författare)
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Next-generation sequencing for viruses in children with rapid-onset type 1 diabetes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 56:8, s. 1705-1711
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Tidskriftsartikel (refereegranskat)abstract
- Viruses are candidate causative agents in the pathogenesis of autoimmune (type 1) diabetes. We hypothesised that children with a rapid onset of type 1 diabetes may have been exposed to such agents shortly before the initiation of islet autoimmunity, possibly at high dose, and thus study of these children could help identify viruses involved in the development of autoimmune diabetes. We used next-generation sequencing to search for viruses in plasma samples and examined the history of infection and fever in children enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY) study who progressed to type 1 diabetes within 6 months from the appearance of islet autoimmunity, and in matched islet-autoantibody-negative controls. Viruses were not detected more frequently in plasma from rapid-onset patients than in controls during the period surrounding seroconversion. In addition, infection histories were found to be similar between children with rapid-onset diabetes and control children, although episodes of fever were reported less frequently in children with rapid-onset diabetes. These findings do not support the presence of viraemia around the time of seroconversion in young children with rapid-onset type 1 diabetes.
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| 9. |
- Virtanen, S. M., et al.
(författare)
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Age at introduction of new foods and advanced beta cell autoimmunity in young children with HLA-conferred susceptibility to type 1 diabetes
- 2006
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Ingår i: Diabetologia. - Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki 00300, Finland. Tampere Univ, Tampere Sch Publ Hlth, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Res Unit, Tampere, Finland. London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, Med Stat Unit, London WC1, England. Finnish Canc Registry, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. : SPRINGER. - 0012-186X .- 1432-0428. ; 49:7, s. 1512-1521
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Evidence for the role of infant feeding in the development of beta cell autoimmunity is inconsistent. We set out to study the effects of breastfeeding and of age at introduction of supplementary foods on the development of beta cell autoimmunity. Subjects and methods: A prospective birth cohort of 3,565 infants with HLA-DQB1-conferred susceptibility to type 1 diabetes was recruited between 1996 and 2001 from two university hospital areas in Finland. Blood samples were collected at 3- to 12-month intervals to measure antibodies against islet cells, insulin, glutamate dehydroxylase and islet antigen 2. The families kept a record on the age at introduction of new foods, and for each visit completed a structured dietary questionnaire. The endpoint was repeated positivity for islet cell antibodies together with at least one of the other three antibodies. Results: The overall or exclusive duration of breastfeeding was not associated with the risk of developing the endpoint. An early age at introduction of fruits and berries (<= 4 months) was related to increased risk of developing positivity for the endpoint (hazard ratio [95% CI] for earliest tertile 2.02 [1.03-3.95] and for midtertile 1.97 [1.06-3.64] compared with latest tertile > 4 months). Also, introducing roots between 3 and 3.9 months (midtertile) was related to increased risk of the endpoint (hazard ratio [95% CI] for the earliest tertile 1.04 [0.57-1.90] and for midtertile 1.82 [1.19-2.79] compared with latest tertile). These associations were independent of several putative socio-demographic and perinatal confounding factors. Conclusions/interpretation: Our findings suggest that an early age at introduction of fruits and berries and roots associates independently with beta cell autoimmunity, contradicting earlier findings from smaller birth cohort studies.
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