| 1. |
- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 2. |
- 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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| 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. |
- Merid, Simon Kebede, et al.
(författare)
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Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age
- 2020
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Ingår i: Genome Medicine. - Stockholm : Karolinska Institutet, Dept of Clinical Science and Education, Södersjukhuset. - 1756-994X.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.
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| 5. |
- Walker, Mike, et al.
(författare)
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Formal definition and dating of the GSSP (Global Stratotype Section and Point) for the base of the Holocene using the Greenland NGRIP ice core, and selected auxiliary records
- 2009
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Ingår i: Journal of Quaternary Science. - : Wiley. - 1099-1417 .- 0267-8179. ; 24:1, s. 3-17
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Forskningsöversikt (refereegranskat)abstract
- The Greenland ice core from NorthGRIP (NGRIP) contains a proxy climate record across the Pleistocene-Holocene boundary of unprecedented clarity and resolution. Analysis of an array of physical and chemical parameters within the ice enables the base of the Holocene, as reflected in the first signs of climatic warming at the end of the Younger Dryas/Greenland Stadial 1 cold phase, to be located with a high degree of precision. This climatic event is most clearly reflected in an abrupt shift in deuterium excess values, accompanied by more gradual changes in delta O-18, dust concentration, a range of chemical species, and annual layer thickness. A timescale based on multi-parameter annual layer counting provides an age of 11 700 calendar yr b2k (before AD 2000) for the base of the Holocene, with a maximum counting error of 99 yr. A proposal that an archived core from this unique sequence should constitute the Global Stratotype Section and Point (GSSP) for the base of the Holocene Series/Epoch (Quaternary System/Period) has been ratified by the International Union of Geological Sciences. Five auxiliary stratotypes for the Pleistocene-Holocene boundary have also been recognised. Copyright (C) 2008 John Wiley & Sons, Ltd.
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| 6. |
- Walker, Mike, et al.
(författare)
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The Global Stratotype Section and Point (GSSP) for the base of the Holocene Series/Epoch (Quaternary System/Period) in the NGRIP ice core
- 2008
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Ingår i: Episodes. - 0705-3797. ; 31:2, s. 264-267
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Tidskriftsartikel (refereegranskat)abstract
- The Greenland ice core from NorthGRIP (NGRIP) contains a proxy climate record across the Pleistocene-Holocene boundary of unprecedented clarity and resolution. Analysis of an array of physical and chemical parameters within the ice enables the base of the Holocene, as reflected in the first signs of climatic warming at the end of the Younger Dryas/Greenland Stadial 1 cold phase, to be located with a high degree of precision. This climatic event is most clearly reflected in an. abrupt shaft in deuterium excess values, accompanied by more gradual changes in delta O-18, dust concentration, a range of chemical species, and annual layer thickness. A timescale based on multi-parameter annual layer counting provides an age of 11,700 yr b2k (before AD2000) for the base of the Holocene, with, an estimated 2 sigma uncertainty of 99 yr: It is proposed that an archived core from this unique sequence should constitute the Global Stratotype Section and Point (GSSP) for the base of the Holocene Series/Epoch (Quaternary System/Period).
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| 7. |
- Barker, Adam, et al.
(författare)
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Association of genetic loci with glucose levels in childhood and adolescence a meta-analysis of over 6,000 children
- 2011
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 60:6, s. 1805-1812
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-To investigate whether associations of common genetic variants recently identified for fasting glucose or insulin levels in nondiabetic adults are detectable in healthy children and adolescents. RESEARCH DESIGN AND METHODS-A total of 16 single nucleotide polymorphisms (SNPs) associated with fasting glucose were genotyped in six studies of children and adolescents of European origin, including over 6,000 boys and girls aged 9-16 years. We performed meta-analyses to test associations of individual SNPs and a weighted risk score of the 16 loci with fasting glucose. RESULTS-Nine loci were associated with glucose levels in healthy children and adolescents, with four of these associations reported in previous studies and five reported here for the first time (GLIS3, PROX1, SLC2A2, ADCY5, and CRY2). Effect sizes were similar to those in adults, suggesting age-independent effects of these fasting glucose loci. Children and adolescents carrying glucose-raising alleles of G6PC2, MTNR1B, GCK, and GLIS3 also showed reduced p-cell function, as indicated by homeostasis model assessment of beta-cell function. Analysis using a weighted risk score showed an increase [beta (95% CI)] in fasting glucose level of 0.026 mrnol/L (0.021-0.031) for each unit increase in the score. CONCLUSIONS-Novel fasting glucose loci identified in genome-wide association studies of adults are associated with altered fasting glucose levels in healthy children and adolescents with effect sizes comparable to adults. In nondiabetic adults, fasting glucose changes little over time, and our results suggest that age-independent effects of fasting glucose loci contribute to long-term interindividual differences in glucose levels from childhood onwards. Diabetes 60:1805-1812, 2011
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| 8. |
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| 9. |
- Walker, Mike, et al.
(författare)
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Formal Subdivision of the Holocene Series/Epoch : A Summary
- 2019
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Ingår i: Journal of the Geological Society of India. - : Springer Science and Business Media LLC. - 0016-7622 .- 0974-6889. ; 93:2, s. 135-141
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Tidskriftsartikel (refereegranskat)abstract
- The Holocene Series/Epoch is the most recent series/epoch in the geological timescale, spanning the interval from 11,700 yr to the present day. Together with the subadjacent Pleistocene, it comprises the Quaternary System/Period. The Holocene record contains diverse geomorphological, biological, climatological and archaeological evidence, within sequences that are often continuous and extremely well-preserved at decadal, annual and even seasonal resolution. As a consequence, the Holocene is perhaps the most intensively-studied series/epoch within the entire Geological Time Scale. Yet until recently little attention had been paid to a formal subdivision of the Holocene. Here we describe an initiative by the Subcommission on Quaternary Stratigraphy (SQS) of the International Commission on Stratigraphy (ICS) to develop a formal stratigraphical subdivision of the Holocene, with three new stages/ages, two underpinned by Global Boundary Stratotype Sections and Points (GSSPs in an ice core, and a third in a speleothem. These stages/ages are defined together with their equivalent subseries/subepochs. The new stages/ages are the Greenlandian with its GSSP in the Greenland NGRIP2 ice core and dated at 11,700 yr b2k (before 2000 CE); the Northgrippian with its GSSP in the Greenland NGRIP1 ice core and dated to 8236 yr b2k; and the Meghalayan, with its GSSP in a speleothem from Mawmluh Cave, northeastern India, with a date of 4250 yr b2k. This subdivision was formally ratified by the Executive Committee of the International Union of Geological Sciences (IUGS) on 14 th June 2018.
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| 10. |
- Walker, Mike, et al.
(författare)
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Subdividing the Holocene Series/Epoch : formalization of stages/ages and subseries/subepochs, and designation of GSSPs and auxiliary stratotypes
- 2019
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Ingår i: Journal of Quaternary Science. - : Wiley. - 0267-8179 .- 1099-1417. ; 34:3, s. 173-186
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Tidskriftsartikel (refereegranskat)abstract
- The Holocene, which currently spans ~11 700 years, is the shortest series/epoch within the geological time scale (GTS), yet it contains a rich archive of evidence in stratigraphical contexts that are frequently continuous and often preserved at high levels of resolution. On 14 June 2018, the Executive Committee of the International Union of Geological Sciences formally ratified a proposal to subdivide the Holocene into three stages/ages, along with their equivalent subseries/subepochs, each anchored by a Global boundary Stratotype Section and Point (GSSP). The new stages are the Greenlandian (Lower/Early Holocene Subseries/Subepoch) with its GSSP in the Greenland NGRIP2 ice core and dated at 11 700 a b2k (before 2000 CE); the Northgrippian (Middle Holocene Subseries/Subepoch) with its GSSP in the Greenland NGRIP1 ice core and dated at 8236 a b2k; and the Meghalayan (Upper/Late Holocene Subseries/Subepoch) with its GSSP in a speleothem from Mawmluh Cave, north-eastern India, with a date of 4250 a b2k. We explain the nomenclature of the new divisions, describe the procedures involved in the ratification process, designate auxiliary stratotypes to support the GSSPs and consider the implications of the subdivision for defining the Anthropocene as a new unit within the GTS.
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