Assessing multivariate gene-metabolome associations with rare variants using Bayesian reduced rank regression

Motivation: A typical genome-wide association study searches for associations between single nucleotide polymorphisms (SNPs) and a univariate phenotype. However, there is a growing interest to investigate associations between genomics data and multivariate phenotypes, for example, in gene expression or metabolomics studies. A common approach is to perform a univariate test between each genotype–phenotype pair, and then to apply a stringent significance cutoff to account for the large number of tests performed. However, this approach has limited ability to uncover dependencies involving multiple variables. Another trend in the current genetics is the investigation of the impact of rare variants on the phenotype, where the standard methods often fail owing to lack of power when the minor allele is present in only a limited number of individuals. Results: We propose a new statistical approach based on Bayesian reduced rank regression to assess the impact of multiple SNPs on a high-dimensional phenotype. Because of the method’s ability to combine information over multiple SNPs and phenotypes, it is particularly suitable for detecting associations involving rare variants. We demonstrate the potential of our method and compare it with alternatives using the Northern Finland Birth Cohort with 4702 individuals, for whom genome-wide SNP data along with lipoprotein profiles comprising 74 traits are available. We discovered two genes (XRCC4 and MTHFD2L) without previously reported associations, which replicated in a combined analysis of two additional cohorts: 2390 individuals from the Cardiovascular Risk in Young Finns study and 3659 individuals from the FINRISK study. Availability and implementation: R-code freely available for download at http://users.ics.aalto.fi/pemartti/gene_metabolome/. Contact: [email protected]; [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

A comparison of sexual behaviour and attitudes of healthy adolescents in a Danish high school in 1982, 1996, and 2001

AIM: To assess changes in sexual behaviour among students at a high school in Denmark from 1982 to 2001. METHODS: An anonymous self-administered questionnaire was used to compare data from three identical cross-sectional surveys performed in 1982, 1996, and 2001. RESULTS: Girls: More girls reported their first sexual intercourse before their 16th birthday in 2001 (42%) than in 1996 (29%) In 1982 it was also 42% (Chi-square for trend: p = 0.003). Fewer girls with no regular partner used condoms for their personal protection in 2001 (2%) than in 1996 (9%) and 1982 (0%) (Chi-square for trend p = 0.016). The proportion of girls with no regular partner who considered protection from sexually transmitted disease important for their choice of contraception was 39% in 2001 compared with 71% in 1996 and only 10% in 1982 (Chi-square for trend: p < 0.0001). Boys: More boys reported sexual debut before their 16th birthday in 2001 (40%) than in 1996 (37%) and 1982 (24%) (Chi-square for trend: p = 0.023). For boys with no regular partner, condom was preferred for personal protection by 85% in 2001, 91% in 1996 and 61% in 1982 (Chi-square for trend p = 0.007). Protection against sexually transmitted infection declined, especially among boys with no regular partner, from 51% in 2001 to 72% in 1996 and 21% in 1982 Chi-square for trend: p < 0.0001). The tendency towards earlier sexual debut and less use of safe sex practices to protect against sexually transmitted infections (STI) was accompanied by a rise in the number of detected STIs during this period. CONCLUSIONS: The period from 1982 to 1996 during which sexual attitudes were directed toward safer sex seems to have given way to a reverse trend in the period from 1996 to 2001. These findings may have significant implications for health care authorities organising preventive strategies for healthy adolescents

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

A Genome-Wide Screen for Interactions Reveals a New Locus on 4p15 Modifying the Effect of Waist-to-Hip Ratio on Total Cholesterol

Peer reviewe

Master of Full Houses : An Analysis of Space as a Social Construction in Emily Brontë’s Wuthering Heights

Uppsatsen granskar två platser i Emily Brontës roman, husen Wuthering Heights och Thruscross Grange. Analysen kretsar kring karaktärerna på dessa platser och relationerna mellan dem med utgångspunkt i Henri Lefebvres teori The Production of Space. Uppsatsen granskar maktperspektiv, äganderätt och olika karaktärers anknytning till hus och hushåll

Master of Full Houses : An Analysis of Space as a Social Construction in Emily Brontë’s Wuthering Heights

Uppsatsen granskar två platser i Emily Brontës roman, husen Wuthering Heights och Thruscross Grange. Analysen kretsar kring karaktärerna på dessa platser och relationerna mellan dem med utgångspunkt i Henri Lefebvres teori The Production of Space. Uppsatsen granskar maktperspektiv, äganderätt och olika karaktärers anknytning till hus och hushåll