| 1. |
- Schmit, Stephanie L, et al.
(author)
-
Novel Common Genetic Susceptibility Loci for Colorectal Cancer.
- 2019
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:2, s. 146-157
-
Journal article (peer-reviewed)abstract
- Background: Previous genome-wide association studies (GWAS) have identified 42 loci (P < 5 × 10-8) associated with risk of colorectal cancer (CRC). Expanded consortium efforts facilitating the discovery of additional susceptibility loci may capture unexplained familial risk.Methods: We conducted a GWAS in European descent CRC cases and control subjects using a discovery-replication design, followed by examination of novel findings in a multiethnic sample (cumulative n = 163 315). In the discovery stage (36 948 case subjects/30 864 control subjects), we identified genetic variants with a minor allele frequency of 1% or greater associated with risk of CRC using logistic regression followed by a fixed-effects inverse variance weighted meta-analysis. All novel independent variants reaching genome-wide statistical significance (two-sided P < 5 × 10-8) were tested for replication in separate European ancestry samples (12 952 case subjects/48 383 control subjects). Next, we examined the generalizability of discovered variants in East Asians, African Americans, and Hispanics (12 085 case subjects/22 083 control subjects). Finally, we examined the contributions of novel risk variants to familial relative risk and examined the prediction capabilities of a polygenic risk score. All statistical tests were two-sided.Results: The discovery GWAS identified 11 variants associated with CRC at P < 5 × 10-8, of which nine (at 4q22.2/5p15.33/5p13.1/6p21.31/6p12.1/10q11.23/12q24.21/16q24.1/20q13.13) independently replicated at a P value of less than .05. Multiethnic follow-up supported the generalizability of discovery findings. These results demonstrated a 14.7% increase in familial relative risk explained by common risk alleles from 10.3% (95% confidence interval [CI] = 7.9% to 13.7%; known variants) to 11.9% (95% CI = 9.2% to 15.5%; known and novel variants). A polygenic risk score identified 4.3% of the population at an odds ratio for developing CRC of at least 2.0.Conclusions: This study provides insight into the architecture of common genetic variation contributing to CRC etiology and improves risk prediction for individualized screening.
|
|
| 2. |
- Livingstone, Katherine M., et al.
(author)
-
FTO genotype and weight loss : systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials
- 2016
-
In: BMJ: British Medical Journal. - : BMJ. - 1756-1833. ; 354
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity.RESULTS: We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category.CONCLUSIONS: We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015969.
|
|
| 3. |
- Mõttus, René, et al.
(author)
-
Comparability of self-reported conscientiousness across 21 countries
- 2012
-
In: European Journal of Personality. - : SAGE Publications. - 1099-0984 .- 0890-2070. ; 26:3, s. 303-317
-
Journal article (peer-reviewed)abstract
- In cross-national studies, mean levels of self-reported phenomena are often not congruent with more objective criteria. One prominent explanation for such findings is that people make self-report judgements in relation to culture-specific standards (often called the reference group effect), thereby undermining the cross-cultural comparability of the judgements. We employed a simple method called anchoring vignettes in order to test whether people from 21 different countries have varying standards for Conscientiousness, a Big Five personality trait that has repeatedly shown unexpected nation-level relationships with external criteria. Participants rated their own Conscientiousness and that of 30 hypothetical persons portrayed in short vignettes. The latter type of ratings was expected to reveal individual differences in standards of Conscientiousness. The vignettes were rated relatively similarly in all countries, suggesting no substantial culture-related differences in standards for Conscientiousness. Controlling for the small differences in standards did not substantially change the rankings of countries on mean self-ratings or the predictive validities of these rankings for objective criteria. These findings are not consistent with mean self-rated Conscientiousness scores being influenced by culture-specific standards. The technique of anchoring vignettes can be used in various types of studies to assess the potentially confounding effects of reference levels.
|
|
| 4. |
- Mõttus, René, et al.
(author)
-
The effect of response style on self-reported conscientiousness across 20 countries.
- 2012
-
In: Personality & Social Psychology Bulletin. - : SAGE Publications. - 0146-1672 .- 1552-7433. ; 38:11, s. 1423-1436
-
Journal article (peer-reviewed)abstract
- Rankings of countries on mean levels of self-reported Conscientiousness continue to puzzle researchers. Based on the hypothesis that cross-cultural differences in the tendency to prefer extreme response categories of ordinal rating scales over moderate categories can influence the comparability of self-reports, this study investigated possible effects of response style on the mean levels of self-reported Conscientiousness in 22 samples from 20 countries. Extreme and neutral responding were estimated based on respondents’ ratings of 30 hypothetical people described in short vignettes. In the vignette ratings, clear cross-sample differences in extreme and neutral responding emerged. These responding style differences were correlated with mean self-reported Conscientiousness scores. Correcting self-reports for extreme and neutral responding changed sample rankings of Conscientiousness, as well as the predictive validities of these rankings for external criteria. The findings suggest that the puzzling country rankings of self-reported Conscientiousness may to some extent result from differences in response styles.
|
|
