Evidence for sex-specific genetic architectures across a spectrum of human complex traits

BACKGROUND: Sex differences are a common feature of human traits; however, the role sex determination plays in human genetic variation remains unclear. The presence of gene-by-sex (GxS) interactions implies that trait genetic architecture differs between men and women. Here, we show that GxS interactions and genetic heterogeneity among sexes are small but common features of a range of high-level complex traits. RESULTS: We analyzed 19 complex traits measured in 54,040 unrelated men and 59,820 unrelated women from the UK Biobank cohort to estimate autosomal genetic correlations and heritability differences between men and women. For 13 of the 19 traits examined, there is evidence that the trait measured is genetically different between males and females. We find that estimates of genetic correlations, based on ~114,000 unrelated individuals and ~19,000 related individuals from the same cohort, are largely consistent. Genetic predictors using a sex-specific model that incorporated GxS interactions led to a relative improvement of up to 4 % (mean 1.4 % across all relevant phenotypes) over those provided by a sex-agnostic model. This further supports the hypothesis of the presence of sexual genetic heterogeneity across high-level phenotypes. CONCLUSIONS: The sex-specific environment seems to play a role in changing genotype expression across a range of human complex traits. Further studies of GxS interactions for high-level human traits may shed light on the molecular mechanisms that lead to biological differences between men and women. However, this may be a challenging endeavour due to the likely small effects of the interactions at individual loci. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-016-1025-x) contains supplementary material, which is available to authorized users

Preparation and uses of chlorinated glycerol derivatives

Crude glycerol (C3H8O3) is a major by-product of biodiesel production from vegetable oils and animal fats. The increased biodiesel production in the last two decades has forced glycerol production up and prices down. However, crude glycerol from biodiesel production is not of adequate purity for industrial uses, including food, cosmetics and pharmaceuticals. The purification process of crude glycerol to reach the quality standards required by industry is expensive and dificult. Novel uses for crude glycerol can reduce the price of biodiesel and make it an economical alternative to diesel. Moreover, novel uses may improve environmental impact, since crude glycerol disposal is expensive and dificult. Glycerol is a versatile molecule with many potential applications in fermentation processes and synthetic chemistry. It serves as a glucose substitute in microbial growth media and as a precursor in the synthesis of a number of commercial intermediates or fine chemicals. Chlorinated derivatives of glycerol are an important class of such chemicals. The main focus of this review is the conversion of glycerol to chlorinated derivatives, such as epichlorohydrin and chlorohydrins, and their further use in the synthesis of additional downstream products. Downstream products include non-cyclic compounds with allyl, nitrile, azide and other functional groups, as well as oxazolidinones and triazoles, which are cyclic compounds derived from ephichlorohydrin and chlorohydrins. The polymers and ionic liquids, which use glycerol as an initial building block, are highlighted, as well.This work was partially funded by the Ministerio de Ciencia, Innovación y Universidades de España (grants: MINECO/FEDER CTQ2015-70982-C3-1-R) and by the Generalitat de Catalunya, Grant 2017 SGR 828, to the Agricultural Biotechnology and Bioeconomy Unit (ABBU)

Synthesis and Thermophysical Characterization of Fatty Amides for Thermal Energy Storage

Nine monoamides were synthesized from carboxylic acids (C8-C18) and crude glycerol. The final monoamides were the result of a rearrangement of the acyl chain during the final hydrogenation process. The purity of the final compounds was determined by spectroscopic and mass spectrometry (MS) techniques. The thermophysical properties of solid monoamides were investigated to determine their capability to act as phase change materials (PCM) in thermal energy storage. Thermophysical properties were determined with a di erential scanning calorimeter (DSC). The melting temperatures of the analyzed material ranged from 62.2 C to 116.4 C. The analyzed enthalpy of these monoamides ranged from 25.8 kJ/kg to 149.7 kJ/kg. Enthalpy values are analyzed considering the carbon chain and the formation of hydrogen bonds.This work was partially funded by the Ministerio de Ciencia, Innovación y Universidades de España (grants: MINECO/FEDER CTQ2015-70982-C3-1-R and MINECO/FEDER RTI2018-093849-B-C31). This work is partially supported by ICREA under the ICREA Academia programme. Acknowledgments: R.C.-G. and L.F.C. would like to thank the Catalan Government for the quality accreditation given to their research groups (grants 2017 SGR 828 and GREiA 2017 SGR 1537, respectively). DBA and GREiA are certified agent TECNIO in the category of technology developers from the Government of Catalonia

Genetic determination of height mediated mate choice

BACKGROUND: Numerous studies have reported positive correlations among couples for height. This suggests that humans find individuals of similar height attractive. However, the answer to whether the choice of a mate with a similar phenotype is genetically or environmentally determined has been elusive. RESULTS: Here we provide an estimate of the genetic contribution to height choice in mates in 13,068 genotyped couples. Using a mixed linear model we show that 4.1 % of the variation in the mate height choice is determined by a person’s own genotype, as expected in a model where one’s height determines the choice of mate height. Furthermore, the genotype of an individual predicts their partners’ height in an independent dataset of 15,437 individuals with 13 % accuracy, which is 64 % of the theoretical maximum achievable with a heritability of 0.041. Theoretical predictions suggest that approximately 5 % of the heritability of height is due to the positive covariance between allelic effects at different loci, which is caused by assortative mating. Hence, the coupling of alleles with similar effects could substantially contribute to the missing heritability of height. CONCLUSIONS: These estimates provide new insight into the mechanisms that govern mate choice in humans and warrant the search for the genetic causes of choice of mate height. They have important methodological implications and contribute to the missing heritability debate. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0833-8) contains supplementary material, which is available to authorized users

GStream:improving SNP and CNV coverage on genome-wide association studies

We present GStream, a method that combines genome-wide SNP and CNV genotyping in the Illumina microarray platform with unprecedented accuracy. This new method outperforms previous well-established SNP genotyping software. More importantly, the CNV calling algorithm of GStream dramatically improves the results obtained by previous state-of-the-art methods and yields an accuracy that is close to that obtained by purely CNV-oriented technologies like Comparative Genomic Hybridization (CGH). We demonstrate the superior performance of GStream using microarray data generated from HapMap samples. Using the reference CNV calls generated by the 1000 Genomes Project (1KGP) and well-known studies on whole genome CNV characterization based either on CGH or genotyping microarray technologies, we show that GStream can increase the number of reliably detected variants up to 25% compared to previously developed methods. Furthermore, the increased genome coverage provided by GStream allows the discovery of CNVs in close linkage disequilibrium with SNPs, previously associated with disease risk in published Genome-Wide Association Studies (GWAS). These results could provide important insights into the biological mechanism underlying the detected disease risk association. With GStream, large-scale GWAS will not only benefit from the combined genotyping of SNPs and CNVs at an unprecedented accuracy, but will also take advantage of the computational efficiency of the method.Postprint (published version