Biology subjects

Christensen, K.

Publications and source records attributed to Christensen, K..

4 recordsLinked to original sources

bioRxiv2018

A novel method for systematic genetic analysis and visualization of phenotypic heterogeneity applied to orofacial clefts

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies may focus on the trait as a whole or on individual subgroups. For example, in orofacial clefting (OFC), three subtypes - cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. It is more challenging, however, to dissect the genetic architecture and describe how a given locus may be contributing to distinct subtypes of a trait. We developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a \"cleft map\" of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 (CP), WNT5A (CLP)), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.

genetics↗

bioRxiv2018

Genome Wide Interaction Studies Identify Sex-Specific Risk Alleles for Nonsyndromic Orofacial Clefts

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene-by-sex (G x S) interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls recruited from 13 countries. First, we performed genome-wide joint tests of the genetic (G) and G x S effects genome-wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test (p < 1.00 x 10-5) by examining the G x S effects from the same model. Out of the 133 loci with suggestive results (p < 1.00 x 10-5) for the joint test, we observed one genome-wide significant G x S effect in the 10q21 locus (rs72804706; p = 6.69 x 10-9; OR = 2.62 [1.89, 3.62]) and 16 suggestive G x S effects. At the intergenic 10q21 locus, the risk of NSCL/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. Our observation that the impact of genetic variants on NSCL/P risk differs for males and females may further our understanding of the genetic architecture of NSCL/P and the sex differences underlying clefts and other birth defects.

genetics↗

bioRxiv2017

Parallel progress in perceived age and life expectancy

Human life expectancy continues to rise in most populations. This rise not only leads to longer lives but is also accompanied by improved health at a given age, i.e. we see a reduction of biological age for a given chronological age in recent cohorts. Despite or even because of the diversity of biomarkers of aging, an accurate quantification of a general shift in biological age across time has been challenging. By comparing age perception of images taken in 2001 over a decade, we show that age perception changes substantially across time and parallels the progress in life expectancy. In 2012, people aged 70+ needed to look 2.3 years younger to be rated the same age as in 2002. Our results further suggest that age perception reflects the past life events better than predicts future length of life, i.e. it is written in your face how much you have aged so far, but does not predict well how fast you will age in the future. We draw this conclusion since age perception among elderly paralleled changes in life expectancy at birth but not changes in remaining life expectancies. We illustrate advantages of perceived age as a biomarker of aging and suggest that changes in age perception should be explored for younger age classes to inform on aging processes, including whether aging is delayed or slowed with increasing life expectancy.

epidemiology↗

bioRxiv2017

Distress tolerance across self-report, behavioral and psychophysiological domains in women with eating disorders and healthy controls

Background and objectivesThe tendency to engage in impulsive behaviors when distressed is linked to engagement in disordered eating. The current study comprehensively examines emotional responses to a distress tolerance task by utilizing self-report, psychophysiological measures (respiratory sinus arrhythmia [RSA], skin conductance responses [SCRs] and tonic skin conductance levels [SCLs]), and behavioral measures (i.e., termination of task, latency to quit task).\n\nMethods26 healthy controls (HCs) and a sample of treatment-seeking women with Bulimia Nervosa (BN), Binge Eating Disorder (BED) and Anorexia Nervosa (AN) (N=106) completed the Paced Auditory Serial Addition Task-Computerized (PASAT-C). Psychophysiological measurements were collected during baseline, PASAT-C, and recovery, then averaged for each time-period. Self-reported emotions were collected at baseline, post-PASAT-C and post-recovery.\n\nResultsOverall, we found an effect of Time, with all participants reporting greater negative emotions, less happiness, lower RSA, more SCRs and higher tonic SCLs after completion of the PASAT-C relative to baseline. There were no differences in PASAT-C performance between groups. There was an effect of Group for negative emotions, with women with BN, BED and AN reporting overall higher levels of negative emotions relative to HCs. Furthermore, we found an effect of Group for greater urges to binge eat and lower RSA values among BED, relative to individuals with BN, AN and HCs.\n\nLimitationsThis study is cross-sectional and lacked an overweight healthy control group.\n\nConclusionDuring the PASAT-C, individuals with EDs compared to HCs report higher levels of negative emotions, despite similar physiological and behavioral manifestations of distress.

physiology↗