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Variants associated with HHIP expression have sexdifferential effects on lung function
<p><strong>Background:</strong> Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females.<br><strong>Methods:</strong> We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium.<br><strong>Results:</strong> Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10<sup>-8</sup>) interactions with sex on lung function, and 21 showed suggestive interactions (P<1x10<sup>-6</sup>). The strongest signal, from rs7697189 (chr4:145436894) on forced expiratory volume in 1 second (FEV<sub>1</sub>) (P=3.15x10<sup>-15</sup>), was replicated (P=0.016) in SpiroMeta. The C allele increased FEV<sub>1</sub> more in males (untransformed FEV<sub>1</sub> β=0.028 [SE 0.0022] litres) than females (β=0.009 [SE 0.0014] litres), and this effect was not accounted for by differential effects on height, smoking or pubertal age. rs7697189 resides upstream of the hedgehog-interacting protein (HHIP) gene and was previously associated with lung function and HHIP lung expression. We found HHIP expression was significantly different between the sexes (P=6.90x10-6), but we could not detect sex differential effects of rs7697189 on expression.<br><strong>Conclusions:</strong> We identified a novel genotype-by-sex interaction at a putative enhancer region upstream of the HHIP gene. Establishing the mechanism by which HHIP SNPs have different effects on lung function in males and females will be important for our understanding of lung health and diseases in both sexes.</p>...
Lipidomic architecture shared by subclinical markers of osteoporosis and atherosclerosis: The Cardiovascular Risk in Young Finns Study
<div>Background</div><div>Studies have shown that osteoporosis and atherosclerosis are comorbid conditions sharing common risk factors and pathophysiological mechanisms. Understanding these is crucial in order to develop ...
Extension of Public Smoking Ban Was Not Associated with Any Immediate Effect on Stroke Occurrence in Finland
We investigated the association between the widening of a nationwide restaurant smoking ban, enacted on 1 June 2007, and stroke admissions. All acute stroke admissions between 1 May 2005 and 30 June 2009 were retrieved ...