| 21. |
- 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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| 22. |
- Vogelezang, Suzanne, et al.
(författare)
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Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes.
- 2022
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Ingår i: BMC medical genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Head circumference is associated with intelligence and tracks from childhood into adulthood.We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age.Seven loci reached genome-wide significance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes.The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.
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| 23. |
- Grant, Struan F A, et al.
(författare)
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Transcription factor 7-like 2 (TCF7L2)
- 2016
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Ingår i: The Genetics of Type 2 Diabetes and Related Traits: Biology, Physiology and Translation. - Cham : Springer International Publishing. - 9783319015743 - 9783319015736 ; , s. 297-316
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Bokkapitel (refereegranskat)abstract
- In 2006 a genetic signal within the gene encoding transcription factor 7-like 2 (TCF7L2) was first reported to be associated with type 2 diabetes. Since then multiple genome-wide association studies have revealed this signal to be among the most strongest associations reported with this disease to date. Furthermore, multiple studies around the world have revealed the global relevance of this locus in intron 3 of the gene and have helped pinpoint, with relative confidence, the causal lesion at this locus. However, despite this association being beyond doubt, there is still a lack of consensus with respect to mechanisms of action and which tissue(s) it actually exerts its influence on the pathogenesis of type 2 diabetes.
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| 24. |
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