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Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline.

ABSTRACT: BACKGROUND:Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined. OBJECTIVES:We aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline. METHODS:We analysed genome-wide data from 4167 individuals from the Busselton Health Study cohort, who had undergone spirometry (12?695 observations across eight time points). A mixed model was fitted and weighted risk scores were calculated for the joint effect of 26 known regions on baseline and longitudinal changes in FEV1 and FEV1/FVC. Potential additional regions of interest were identified and followed up in two independent cohorts. RESULTS:The 26 regions previously associated with cross-sectional lung function jointly showed a strong effect on baseline lung function (p=4.44×10-16 for FEV1/FVC) but no effect on longitudinal decline (p=0.160 for FEV1/FVC). This was replicated in an independent cohort. 39 additional regions of interest (48 variants) were identified; these associations were not replicated in two further cohorts. CONCLUSIONS:Previously identified genetic variants jointly have a strong effect on cross-sectional lung function in adults but little or no effect on the rate of decline of lung function. It is possible that they influence COPD risk through lung development. Although no genetic variants have yet been associated with lung function decline at stringent genome-wide significance, longitudinal change in lung function is heritable suggesting that there is scope for future discoveries.

SUBMITTER: John C

PROVIDER: S-EPMC5520280 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline.

John Catherine C Soler Artigas María M Hui Jennie J Nielsen Sune Fallgaard SF Rafaels Nicholas N Paré Peter D PD Hansel Nadia N NN Shrine Nick N Kilty Iain I Malarstig Anders A Jelinsky Scott A SA Vedel-Krogh Signe S Barnes Kathleen K Hall Ian P IP Beilby John J Musk Arthur W AW Nordestgaard Børge G BG James Alan A Wain Louise V LV Tobin Martin D MD

Thorax 20170207 5

<h4>Background</h4>Genome-wide association studies have identified numerous genetic regions that influence cross-sectional lung function. Longitudinal decline in lung function also includes a heritable component but the genetic determinants have yet to be defined.<h4>Objectives</h4>We aimed to determine whether regions associated with cross-sectional lung function were also associated with longitudinal decline and to seek novel variants which influence decline.<h4>Methods</h4>We analysed genome- ...[more]

PMID: 28174340

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Project description:BackgroundThyroid function may be a factor affecting kidney function in the general population. Kidney and thyroid function vary with age; therefore, the association between thyroid function and decreased kidney function in older adults may be different from that in younger adults and remains controversial. This study aimed to estimate the association between normal-range thyroid function and age-related decline in kidney function in older Chinese adults.MethodsA total of 15,653 adults, of whom 23.2% (N = 3624) were older adults (age≧65 years), were collected at the Health Management Center of the First Affiliated Hospital of Nanjing Medical University from January 2018 to January 2020. Basic demographic information was collected by a physician-administered questionnaire. The estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula. Trends in thyroid function with age were shown by means of free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) in subgroups every ten years. The association between kidney function and thyroid function was estimated by multiple linear regression using β value and by multivariable logistic regression models using odds ratios (OR) after adjusting for age, gender, body mass index, and serum urine acid.ResultsIn the older population, TSH tended to increase with age and FT3 tended to decrease, whereas FT4 was relatively stable. eGFR decreased significantly with increasing TSH (β = -0.081) and decreasing FT3 (β = 0.083) concentrations. Compared with those in the lowest quartile of FT3 (3.10-4.47 pmol/L), the prevalence of eGFR < 75 ml/min/1.73m2 decreased significantly by 22.0% for those with FT3 of 4.47-4.81 pmol/L, 27.6% for those with FT3 of 4.82-5.20 pmol/L, and 34.9% for those with FT3 of 5.21-6.8 pmol/L in older individuals (P for trend < .001). The OR was 1.315 (P: 0.025) in subjects with high-normal TSH, using low-normal TSH as a reference. The prevalence of reduced kidney function was not significantly associated with FT4 within the reference range. Similar results were found in association between the prevalence of eGFR < 60 ml/min/1.73m2 and thyroid function.ConclusionsThis study demonstrated a significant association between kidney function and thyroid function, particularly FT3, in the older population. Clinicians may need to pay more attention to the assessment and follow-up of kidney function in older individuals with low-normal FT3 and high-normal TSH.

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Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline.

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Genetic variants affecting cross-sectional lung function in adults show little or no effect on longitudinal lung function decline.

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