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Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
Thin diamond foils are needed in many particle accelerator experiments regarding nuclear and atomic physics, as well as in some interdisciplinary research. Particularly, nanodiamond texture is attractive for this purpose as it possesses a unique combination of diamond properties such as high thermal conductivity, mechanical strength and high radiation hardness; therefore, it is a potential material for energetic ion beam stripper foils. At the ORNL Spallation Neutron Source (SNS), the installed set of foils must be able to survive a nominal five-month operation period, without the need for unscheduled costly shutdowns and repairs. Thus, a single nanodiamond foil about the size of a postage stamp is critical to the entire operation of SNS and similar sources in U.S. laboratories and around the world. We are investigating nanocrystalline, polycrystalline and their admixture films fabricated using a hot filament chemical vapor deposition (HFCVD) system for H- stripping to support the SNS at Oak Ridge National Laboratory. Here we discuss optimization of process variables such as substrate temperature, process gas ratio of H2/Ar/CH4, substrate to filament distance, filament temperature, carburization conditions, and filament geometry to achieve high purity diamond foils on patterned silicon substrates with manageable intrinsic and thermal stresses so that they can be released as free standing foils without curling. An in situ laser reflectance interferometry tool (LRI) is used for monitoring the growth characteristics of the diamond thin film materials. The optimization process has yielded free standing foils with no pinholes. The sp3/sp2 bonds are controlled to optimize electrical resistivity to reduce the possibility of surface charging of the foils. The integrated LRI and HFCVD process provides real time information on the growth of films and can quickly illustrate growth features and control over film thickness. The results are discussed in the light of development of nanodiamond foils that will be able to withstand a few MW proton beam and hopefully will be able to be used after possible future upgrades to the SNS to greater than a 3MW beam.
It is with deep sadness that we report the passing of our friend and colleague Arnold Kanter on April 10, 2010, at the all-too-young age of 65. He died from acute myelogenous leukemia, diagnosed in 2007.