Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

The Kepler-10 Planetary System Revisited by HARPS-N: A Hot Rocky World and a Solid Neptune-Mass Planet

Kepler-10b was the first rocky planet detected by the Kepler satellite and confirmed with radial velocity follow-up observations from Keck-HIRES. The mass of the planet was measured with a precision of around 30%, which was
insufficient to constrain models of its internal structure and composition in detail. In addition to Kepler-10b, a second planet transiting the same star with a period of 45 days was statistically validated, but the radial velocities were only
good enough to set an upper limit of 20 M⊕ for the mass of Kepler-10c. To improve the precision on the mass for planet b, the HARPS-N Collaboration decided to observe Kepler-10 intensively with the HARPS-N spectrograph
on the Telescopio Nazionale Galileo on La Palma. In total, 148 high-quality radial-velocity measurements were obtained over two observing seasons. These new data allow us to improve the precision of the mass determination for Kepler-10b to 15%. With a mass of 3.33 ± 0.49 M⊕ and an updated radius of 1.47+0.03 −0.02 R⊕, Kepler-10b has a density of 5.8 ± 0.8 g cm−3, very close to the value predicted by models with the same internal structure and composition as the Earth. We were also able to determine a mass for the 45-day period planet Kepler-10c, with an even better precision of 11%. With a mass of 17.2 ± 1.9 M⊕ and radius of 2.35+0.09 −0.04 R⊕, Kepler-10c has a density of 7.1 ± 1.0 g cm−3. Kepler-10c appears to be the first strong evidence of a class of more massive solid planets with longer orbital periods

Invading and expanding: range dynamics and ecological consequences of the greater white-toothed shrew (Crocidura russula) invasion in Ireland

Establishing how invasive species impact upon pre-existing species is a fundamental question in ecology and conservation biology. The greater white-toothed shrew (Crocidura russula) is an invasive species in Ireland that was first recorded in 2007 and which, according to initial data, may be limiting the abundance/distribution of the pygmy shrew (Sorex minutus), previously Ireland’s only shrew species. Because of these concerns, we undertook an intensive live-trapping survey (and used other data from live-trapping, sightings and bird of prey pellets/nest inspections collected between 2006 and 2013) to model the distribution and expansion of C. russula in Ireland and its impacts on Ireland’s small mammal community. The main distribution range of C. russula was found to be approximately 7,600 km2 in 2013, with established outlier populations suggesting that the species is dispersing with human assistance within the island. The species is expanding rapidly for a small mammal, with a radial expansion rate of 5.5 km/yr overall (2008–2013), and independent estimates from live-trapping in 2012–2013 showing rates of 2.4–14.1 km/yr, 0.5–7.1 km/yr and 0–5.6 km/yr depending on the landscape features present. S. minutus is negatively associated with C. russula. S. minutus is completely absent at sites where C. russula is established and is only present at sites at the edge of and beyond the invasion range of C. russula. The speed of this invasion and the homogenous nature of the Irish landscape may mean that S. minutus has not had sufficient time to adapt to the sudden appearance of C. russula. This may mean the continued decline/disappearance of S. minutus as C. russula spreads throughout the island.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.