@article {6368, title = {Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of European descent confirm known loci and reveal several novel associations.}, journal = {Hum Mol Genet}, volume = {23}, year = {2014}, month = {2014 May 01}, pages = {2498-510}, abstract = {

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI{\textquoteright}s Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes \~{}50 000 cosmopolitan tagged SNPs across \~{}2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 {\texttimes} 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β {\textpm} SE, 0.048 {\textpm} 0.008, P = 7.7 {\texttimes} 10(-9)) as was rs7302703-G in HOXC10 (β = 0.044 {\textpm} 0.008, P = 2.9 {\texttimes} 10(-7)) and rs936108-C in PEMT (β = 0.035 {\textpm} 0.007, P = 1.9 {\texttimes} 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β = 0.10 {\textpm} 0.02, P = 1.9 {\texttimes} 10(-6)) and rs1037575-A in ATBDB4 (β = 0.046 {\textpm} 0.01, P = 2.2 {\texttimes} 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

}, keywords = {Adiposity, Adult, Aged, Aged, 80 and over, Body Mass Index, European Continental Ancestry Group, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Waist Circumference, Waist-Hip Ratio, Young Adult}, issn = {1460-2083}, doi = {10.1093/hmg/ddt626}, author = {Yoneyama, Sachiko and Guo, Yiran and Lanktree, Matthew B and Barnes, Michael R and Elbers, Clara C and Karczewski, Konrad J and Padmanabhan, Sandosh and Bauer, Florianne and Baumert, Jens and Beitelshees, Amber and Berenson, Gerald S and Boer, Jolanda M A and Burke, Gregory and Cade, Brian and Chen, Wei and Cooper-Dehoff, Rhonda M and Gaunt, Tom R and Gieger, Christian and Gong, Yan and Gorski, Mathias and Heard-Costa, Nancy and Johnson, Toby and Lamonte, Michael J and McDonough, Caitrin and Monda, Keri L and Onland-Moret, N Charlotte and Nelson, Christopher P and O{\textquoteright}Connell, Jeffrey R and Ordovas, Jose and Peter, Inga and Peters, Annette and Shaffer, Jonathan and Shen, Haiqinq and Smith, Erin and Speilotes, Liz and Thomas, Fridtjof and Thorand, Barbara and Monique Verschuren, W M and Anand, Sonia S and Dominiczak, Anna and Davidson, Karina W and Hegele, Robert A and Heid, Iris and Hofker, Marten H and Huggins, Gordon S and Illig, Thomas and Johnson, Julie A and Kirkland, Susan and K{\"o}nig, Wolfgang and Langaee, Taimour Y and McCaffery, Jeanne and Melander, Olle and Mitchell, Braxton D and Munroe, Patricia and Murray, Sarah S and Papanicolaou, George and Redline, Susan and Reilly, Muredach and Samani, Nilesh J and Schork, Nicholas J and van der Schouw, Yvonne T and Shimbo, Daichi and Shuldiner, Alan R and Tobin, Martin D and Wijmenga, Cisca and Yusuf, Salim and Hakonarson, Hakon and Lange, Leslie A and Demerath, Ellen W and Fox, Caroline S and North, Kari E and Reiner, Alex P and Keating, Brendan and Taylor, Kira C} } @article {7586, title = {Leisure-time physical activity and leukocyte telomere length among older women.}, journal = {Exp Gerontol}, volume = {95}, year = {2017}, month = {2017 Sep}, pages = {141-147}, abstract = {

BACKGROUND: Shortened leukocyte telomere length (LTL), a purported marker of cellular aging, is associated with morbidity and mortality. However, the association of physical activity, a modifiable lifestyle behavior, with LTL has not been adequately studied among older adults.

METHODS: In this cross-sectional study, we examined associations of various intensity levels of leisure-time physical activity with LTL among 1476 older white and African American women from the Women{\textquoteright}s Health Initiative Objective Physical Activity and Cardiovascular Health study. Self-reported physical activity was assessed by questionnaire, and LTL was measured by Southern blot. The association between physical activity and LTL was evaluated using multiple linear regression models adjusted for demographic characteristics, lifestyle behaviors, and health-related variables.

RESULTS: Women were on average aged 79.2 (standard deviation 6.7) years old. In the final model adjusted for age, race/ethnicity, education, marital status, smoking, alcohol, body mass index, a history of chronic diseases, and hormone therapy use, LTL was on average 110 (95\% confidence interval, 20-190) base pairs longer among women in the highest (>=17.00MET-hours/week) compared with the lowest (<1.25MET-hours/week) level of total leisure-time physical activity (P for trend=0.02). Higher levels of moderate-to-vigorous physical activity (P for trend=0.04) and faster walking speed (P for trend=0.03) were also associated with longer LTL in the fully-adjusted models.

CONCLUSION: Older women participating in greater amounts of total leisure-time physical activity and moderate-to-vigorous physical activity had longer LTL.

}, issn = {1873-6815}, doi = {10.1016/j.exger.2017.05.019}, author = {Shadyab, Aladdin H and Lamonte, Michael J and Kooperberg, Charles and Reiner, Alexander P and Carty, Cara L and Manini, Todd M and Hou, Lifang and Di, Chongzhi and Macera, Caroline A and Gallo, Linda C and Shaffer, Richard A and Jain, Sonia and LaCroix, Andrea Z} } @article {9917, title = {Association Between Cigarette Smoking~and Subclinical Markers of Cardiovascular Harm.}, journal = {J Am Coll Cardiol}, volume = {85}, year = {2025}, month = {2025 Mar 18}, pages = {1018-1034}, abstract = {

BACKGROUND: Cigarette smoking is a strong risk factor for cardiovascular harm.

OBJECTIVES: The study sought to explore the detailed relationships between smoking intensity, pack-years, and~time since cessation with inflammation, thrombosis, and subclinical atherosclerosis markers of cardiovascular harm.

METHODS: We included 182,364 participants (mean age 58.2 years, 69.0\% female) from 22 cohorts of the Cross Cohort Collaboration with self-reported smoking status, including smoking intensity and/or pack-years, and concurrent subclinical marker measurements. Markers were categorized into 3 domains: inflammation (high-sensitivity C-reactive protein, interleukin-6, glycoprotein acetylation), thrombosis (fibrinogen, D-dimer), and subclinical atherosclerosis (coronary artery calcium, carotid intima-media thickness, carotid plaque, and ankle-brachial index). Utilizing multivariate regression models and restricted cubic splines, we assessed associations of smoking status, intensity, pack-years, time since cessation, and subclinical markers.

RESULTS: A total of 15.3\% of participants currently smoke (mean 16.7 cigarettes/day, mean 30.0 pack-years), and 34.6\% of participants formerly smoked (median 19.0 years since quitting, mean 22.4 pack-years). Participants with a history of smoking showed higher levels of all subclinical markers compared with those who have never smoked, with stronger associations observed in those currently smoke. Among participants who currently smoke, smoking intensity showed a clear dose-response relationship with all markers, except for D-dimer, specifically with incremental 1\% to 9\% higher levels of subclinical markers per 10 cigarettes. After 20 cigarettes, the patterns appeared to plateau for blood markers, while they continued to increase for atherosclerosis markers. Among those who have ever smoked, robust dose-response relationships were observed for pack-years with all subclinical markers, with incremental 1\% to 9\% higher levels per 10 pack-years. The dose-response effects persisted after 20 pack-years for all markers, though with a milder slope. Among participants who smoked formerly, there were substantially lower levels of biomarkers with longer time since quitting, and most markers were not different compared with those who have never smoked by 30 years, except for the coronary artery calcium score, which remained 19\% higher even beyond quitting after 30 years.

CONCLUSIONS: Smoking-relevant parameters show strong and dose-response relationships across 3 domains of subclinical markers of cardiovascular harm. The sensitivity of the tested subclinical markers to small increments in cigarette exposure suggests potential value in the regulation of new and existing tobacco products.

}, keywords = {Aged, Atherosclerosis, Biomarkers, Cardiovascular Diseases, Carotid Intima-Media Thickness, Cigarette Smoking, Cohort Studies, Female, Humans, Male, Middle Aged, Risk Factors}, issn = {1558-3597}, doi = {10.1016/j.jacc.2024.12.032}, author = {Yao, Zhiqi and Tasdighi, Erfan and Dardari, Zeina A and Jha, Kunal K and Osuji, Ngozi and Rajan, Tanuja and Boakye, Ellen and Rodriguez, Carlos J and Matsushita, Kunihiro and Simonsick, Eleanor M and Lima, Jo{\~a}o A C and Widome, Rachel and Cohen, Debbie L and Appel, Lawrence J and Khera, Amit and Hall, Michael E and Judd, Suzanne E and Cole, Shelley A and Vasan, Ramachandran S and Benjamin, Emelia J and Lotufo, Paulo A and Bensenor, Isabela M and El Khoudary, Samar R and Barinas-Mitchell, Emma and Janssen, Imke and Psaty, Bruce M and Eaton, Charles B and Lamonte, Michael J and Cawthon, Peggy M and Orwoll, Eric S and Irvin, Marguerite R and Bhatnagar, Aruni and DeFilippis, Andrew P and El-Shahaway, Omar and Blaha, Michael J} }