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Genomic architecture of asthma differs by sex.

ABSTRACT: Asthma comprised of highly heterogeneous subphenotypes resulting from complex interplay between genetic and environmental stimuli. While much focus has been placed on extrinsic environmental stimuli, intrinsic environment such as sex can interact with genes to influence asthma risk. However, few studies have examined sex-specific genetic effects. The overall objective of this study was to evaluate if sex-based differences exist in genomic associations with asthma. We tested 411 asthmatics and 297 controls for presence of interactions and sex-stratified effects in 51 genes using both SNP and gene expression data. Logistic regression was used to test for association. Over half (55%) of the genetic variants identified in sex-specific analyses were not identified in the sex-combined analysis. Further, sex-stratified genetic analyses identified associations with significantly higher median effect sizes than sex-combined analysis for girls (p-value=6.5E-15) and for boys (p-value=1.0E-7). When gene expression data were analyzed to identify genes that were differentially expressed in asthma versus non-asthma, nearly one third (31%) of the probes identified in the sex-specific analyses were not identified in the sex-combined analysis. Both genetic and gene expression data suggest that the biologic underpinnings for asthma may differ by sex. Failure to recognize sex interactions in asthma greatly decreases the ability to detect significant genomic variation and may result in significant misrepresentation of genes and pathways important in asthma in different environments.

SUBMITTER: Mersha TB

PROVIDER: S-EPMC4458428 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Genomic architecture of asthma differs by sex.

Mersha Tesfaye B TB Martin Lisa J LJ Biagini Myers Jocelyn M JM Kovacic Melinda Butsch MB He Hua H Lindsey Mark M Sivaprasad Umasundari U Chen Weiguo W Khurana Hershey Gurjit K GK

Genomics 20150325 1

Asthma comprised of highly heterogeneous subphenotypes resulting from complex interplay between genetic and environmental stimuli. While much focus has been placed on extrinsic environmental stimuli, intrinsic environment such as sex can interact with genes to influence asthma risk. However, few studies have examined sex-specific genetic effects. The overall objective of this study was to evaluate if sex-based differences exist in genomic associations with asthma. We tested 411 asthmatics and 29 ...[more]

PMID: 25817197

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Project description:IntroductionLate onset Alzheimer's disease (AD) is the most common form of dementia, in which almost 70% of patients are women.HypothesisWe hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women.MethodsWe studied cognitively healthy individuals from the Alzheimer's Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of APOE E4. Linear mixed effect models with covariates (education, handedness, presence of apolipoprotein [APOE] E4 and intra-subject effect) were utilized to evaluate sex differences. The associations of verbal learning and memory abilities with topological network properties were assessed.ResultWomen had a significantly lower magnitude of the global and regional functional network metrics compared to men. Exploratory association analysis showed that higher global clustering coefficient was associated with lower percent forgetting in women and worse cognitive scores in men.ConclusionWomen overall show lower magnitude on measures of resting state functional network topology and connectivity. This factor can play a role in their different vulnerability to AD.Significance statementTwo thirds of AD patients are women but the reasons for these sex difference are not well understood. When this late onset form dementia arises is too late to understand the potential causes of this sex disparities. Studies on cognitively healthy elderly population are a fundamental approach to explore in depth this different vulnerability to the most common form of dementia, currently affecting 6.2 million Americans aged 65 and older are, which means that >1 in 9 people (11.3%) 65 and older are affected by AD. Approaches such as resting-state functional network topology and connectivity may play a key role in understanding and elucidate sex-dependent differences relevant to late-onset dementia syndromes.

Dataset Information

Genomic architecture of asthma differs by sex.

Publications

Genomic architecture of asthma differs by sex.

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