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- Willer, Cristen J., et al.
(författare)
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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
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| 2. |
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| 3. |
- Weedon, Michael N., et al.
(författare)
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A common variant of HMGA2 is associated with adult and childhood height in the general population
- 2007
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 39:10, s. 1245-1250
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Tidskriftsartikel (refereegranskat)abstract
- Human height is a classic, highly heritable quantitative trait. To begin to identify genetic variants influencing height, we examined genome-wide association data from 4,921 individuals. Common variants in the HMGA2 oncogene, exemplified by rs1042725, were associated with height (P= 4x10(-8)). HMGA2 is also a strong biological candidate for height, as rare, severe mutations in this gene alter body size in mice and humans, so we tested rs1042725 in additional samples. We confirmed the association in 19,064 adults from four further studies (P= 3x10(-11), overall P= 4x10(-16), including the genome-wide association data). We also observed the association in children (P=1x 10(-6), N= 6,827) and a tall/short case-control study (P= 4x10(-6), N=3,207). We estimate that rs1042725 explains similar to 0.3% of population variation in height (similar to 0.4 cm increased adult height per C allele). There are few examples of common genetic variants reproducibly associated with human quantitative traits; these results represent, to our knowledge, the first consistently replicated association with adult and childhood height.
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| 4. |
- Charakida, M., et al.
(författare)
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Endothelial dysfunction in childhood infection
- 2005
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Ingår i: Circulation. - 1524-4539. ; 111:13, s. 1660-5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atherosclerosis begins in early life, and endothelial dysfunction is recognized as a key initiating event in the development of atherosclerosis. Although infection has been implicated in endothelial dysfunction and atherogenesis, the impact of acute common childhood infections on the vascular endothelium is unknown. METHODS AND RESULTS: We studied 600 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. The children were divided into 3 groups: those with current acute infection (AI; n=135; 73 boys and 62 girls); a convalescent group with infection in the past 2 weeks (n=166; 78 boys and 88 girls), and a healthy control group (n=299; 131 boys and 168 girls). Endothelial function was determined in all subjects by high-resolution ultrasound to measure brachial artery flow-mediated dilation (FMD) and was expressed as the percentage change in diameter from baseline after reactive hyperemia. FMD was repeated in 40 children in the AI group and 50 in the control group after a mean interval of 1 year. FMD was lower in both the AI group (6.3+/-2.7%, mean+/-SD) and the convalescent group (8.1+/-3.1%) than in the control group (9.7+/-2.5%; P<0.001 for both). The observed differences in FMD remained after adjustment for potential confounding variables. At the repeat visit, FMD was unchanged in controls (P=0.85) but improved in the AI group (P<0.001). CONCLUSIONS: Acute infection in childhood is associated with impaired endothelium-dependent vasodilation. These findings support a potential role for previously unsuspected extrinsic inflammatory stimuli in the pathogenesis of early atherosclerosis.
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| 5. |
- Ong, Ken K., et al.
(författare)
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Genetic variation in LIN28B is associated with the timing of puberty
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:6, s. 729-733
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Tidskriftsartikel (refereegranskat)abstract
- The timing of puberty is highly variable(1). We carried out a genome-wide association study for age at menarche in 4,714 women and report an association in LIN28B on chromosome 6 (rs314276, minor allele frequency (MAF) = 0.33, P = 1.5 x 10(-8)). In independent replication studies in 16,373 women, each major allele was associated with 0.12 years earlier menarche (95% CI = 0.08-0.16; P = 2.8 x 10(-10); combined P = 3.6 x 10(-16)). This allele was also associated with earlier breast development in girls (P = 0.001; N = 4,271); earlier voice breaking (P = 0.006, N = 1,026) and more advanced pubic hair development in boys (P = 0.01; N = 4,588); a faster tempo of height growth in girls (P = 0.00008; N = 4,271) and boys (P = 0.03; N = 4,588); and shorter adult height in women (P = 3.6 x 10(-7); N = 17,274) and men (P = 0.006; N = 9,840) in keeping with earlier growth cessation. These studies identify variation in LIN28B, a potent and specific regulator of microRNA processing(2), as the first genetic determinant regulating the timing of human pubertal growth and development.
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| 7. |
- Barrett, S. C. H., et al.
(författare)
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Evolutionary pathways to self-fertilization in a tristylous plant species
- 2009
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Ingår i: New Phytologist. - 0028-646X .- 1469-8137. ; 183:3, s. 546-556
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Tidskriftsartikel (refereegranskat)abstract
- P>Evolutionary transitions from outcrossing to selfing occur commonly in heterostylous genera. The morphological polymorphisms that characterize heterostyly provide opportunities for different pathways for selfing to evolve. Here, we investigate the origins and pathways by which selfing has evolved in tristylous Eichhornia paniculata by providing new evidence based on morphology, DNA sequences and genetic analysis. The primary pathway from outcrossing to selfing involves the stochastic loss of the short-styled morph (S-morph) from trimorphic populations, followed by the spread of selfing variants of the mid-styled morph (M-morph). However, the discovery of selfing variants of the long-styled morph (L-morph) in Central America indicates a secondary pathway and distinct origin for selfing. Comparisons of multi-locus nucleotide sequences from 27 populations sampled from throughout the geographical range suggest multiple transitions to selfing. Genetic analysis of selfing variants of the L- and M-morphs demonstrates recessive control of the loss of herkogamy, although the number of factors appears to differ between the forms. Early stages in the establishment of selfing involve developmental instability in the formation of flowers capable of autonomous self-pollination. The relatively simple genetic control of herkogamy reduction and frequent colonizing episodes may often create demographic conditions favouring transitions to selfing in E. paniculata. New Phytologist (2009) 183: 546-556doi: 10.1111/j.1469-8137.2009.02937.x.
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