A Genome-Wide Association Study Identifies rs2000999 as a Strong Genetic Determinant of Circulating Haptoglobin Levels

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far

Adolescent Participation in Sport and Adult Physical Activity

Background: Physical activity in adolescence has been reported to enhance physical activity in adulthood, but detailed information on the enhancing effect of different types of adolescent sports is lacking. We evaluated the association between participation in different types of adolescent sports and physical activity in adulthood. Methods: The sample comprised 7794 males and females who responded to the mailed questions on physical activity status at age 14 years and at age 31 years in follow-up surveys of the Northern Finland 1966 birth cohort. The associations between adolescent participation in different sports and adult physical activity was examined by multinomial logistic regression. Results: Frequent participation in sports after school hours in adolescence was associated with a high level of physical activity in adulthood. In males, adolescent participation in ball games, intensive endurance sports, track and field, and combat sports was associated with a high or very high level of adult activity. In females, the same applied to adolescent participation in running, orienteering, track and field, cycling, gymnastics, and riding. Adolescent participation in ball games increased participation in ball games in adulthood, especially in males, while participation in cross-country skiing, running, and orienteering provided the greatest stimulation to carry over of some endurance sport to adulthood. Conclusions: Participation in sports at least once a week among females and twice a week among males was associated with high level of physical activity in later life. Adolescent participation in the intensive endurance sports, and some sports that require and encourage diversified sports skills, appeared to be most beneficial with respect to the enhancement of adult physical activity

Inferring combined CNV/SNP haplotypes from genotype data

Motivation: Copy number variations (CNVs) are increasingly recognized as an substantial source of individual genetic variation, and hence there is a growing interest in investigating the evolutionary history of CNVs as well as their impact on complex disease susceptibility. CNV/SNP haplotypes are critical for this research, but although many methods have been proposed for inferring integer copy number, few have been designed for inferring CNV haplotypic phase and none of these are applicable at genome-wide scale. Here, we present a method for inferring missing CNV genotypes, predicting CNV allelic configuration and for inferring CNV haplotypic phase from SNP/CNV genotype data. Our method, implemented in the software polyHap v2.0, is based on a hidden Markov model, which models the joint haplotype structure between CNVs and SNPs. Thus, haplotypic phase of CNVs and SNPs are inferred simultaneously. A sampling algorithm is employed to obtain a measure of confidence/credibility of each estimate

A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk

In genome-wide association (GWA) data from 2,151 nondiabetic French subjects, we identified rs1387153, near MTNR1B (which encodes the melatonin receptor 2 (MT2)), as a modulator of fasting plasma glucose (FPG; P = 1.3 x 10(-7)). In European populations, the rs1387153 T allele is associated with increased FPG (beta = 0.06 mmol/l, P = 7.6 x 10(-29), N = 16,094), type 2 diabetes (T2D) risk (odds ratio (OR) = 1.15, 95% CI = 1.08-1.22, P = 6.3 x 10(-5), cases N = 6,332) and risk of developing hyperglycemia or diabetes over a 9-year period (hazard ratio (HR) = 1.20, 95% CI = 1.06-1.36, P = 0.005, incident cases N = 515). RT-PCR analyses confirm the presence of MT2 transcripts in neural tissues and show MT2 expression in human pancreatic islets and beta cells. Our data suggest a possible link between circadian rhythm regulation and glucose homeostasis through the melatonin signaling pathway

Manhattan plot of the GWAS of the discovery cohort comprising 631 children.

<p><b>A</b>, A Manhattan plot showing the −log₁₀(<i>P</i> values) of SNPs from the association analysis of the 631 SFS children from stage 1. <b>B</b>, An overview of the −log₁₀(<i>P</i> values) of Chromosome 16. <b>C</b>, The genomic region of the 618 LD block displayed in UCSC Genome Browser.</p

Estimates of familial correlations ± standard error for serum haptoglobin concentration (656 familles/2680 individuals).

<p>* <i>P</i>≤0.05, ** <i>P</i>≤0.01, *** <i>P</i>≤0.001: compared to zero.</p><p>Model 1 estimated all eight correlations without adjustment.</p><p>Model 2 estimated all eight correlations with adjustment for age and BMI,</p><p>Model 3 estimated three correlations with adjustment for age and BMI with no gender effect on parent or offspring correlations: FS = MS = MD = FD and SS = SD = DD.</p><p>Model 4 estimated three correlations with adjustment for age, BMI and rs2000999 allelic frequency with no gender effect on parent or offspring correlations: FS = MS = MD = FD and SS = SD = DD.</p><p>Values in brackets were constrained to be equal to a preceding value according to the hypotheses of the model.</p><p>BMI: body mass index.</p

Variance components of serum haptoglobin concentrations (656 families/2680 individuals, rs2000999 & rs4788597 as allelic frequency).

*<p><i>P</i>≤0.05,</p>**<p><i>P</i>≤0.01,</p><p>*** <i>P</i>≤0.001.</p><p>BMI: body mass index.</p