ORCID Profile
0000-0002-8349-3028
Current Organisations
IT University of Copenhagen
,
Københavns Universitet
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Publisher: Springer Science and Business Media LLC
Date: 24-04-2014
Publisher: Public Library of Science (PLoS)
Date: 06-06-2013
Publisher: Elsevier BV
Date: 04-2011
Abstract: High birth weight is associated with adult body mass index (BMI). We hypothesized that birth weight and BMI may partly share a common genetic background. The objective was to examine the associations of 12 established BMI variants in or near the NEGR1, SEC16B, TMEM18, ETV5, GNPDA2, BDNF, MTCH2, BCDIN3D, SH2B1, FTO, MC4R, and KCTD15 genes and their additive score with birth weight. A meta-analysis was conducted with the use of 1) the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk, Hertfordshire, Fenland, and European Youth Heart Study cohorts (n(max) = 14,060) 2) data extracted from the Early Growth Genetics Consortium meta-analysis of 6 genome-wide association studies for birth weight (n(max) = 10,623) and 3) all published data (n(max) = 14,837). Only the MTCH2 and FTO loci showed a nominally significant association with birth weight. The BMI-increasing allele of the MTCH2 variant (rs10838738) was associated with a lower birth weight (β ± SE: -13 ± 5 g/allele P = 0.012 n = 23,680), and the BMI-increasing allele of the FTO variant (rs1121980) was associated with a higher birth weight (β ± SE: 11 ± 4 g/allele P = 0.013 n = 28,219). These results were not significant after correction for multiple testing. Obesity-susceptibility loci have a small or no effect on weight at birth. Some evidence of an association was found for the MTCH2 and FTO loci, ie, lower and higher birth weight, respectively. These findings may provide new insights into the underlying mechanisms by which these loci confer an increased risk of obesity.
Publisher: American Diabetes Association
Date: 26-02-2015
DOI: 10.2337/DB14-1629
Abstract: The FTO gene harbors variation with the strongest effect on adiposity and obesity risk. Previous data support a role for FTO variation in influencing food intake. We conducted a combined analysis of 16,094 boys and girls aged 1–18 years from 14 studies to examine the following: 1) the association between the FTO rs9939609 variant (or a proxy) and total energy and macronutrient intake and 2) the interaction between the FTO variant and dietary intake, and the effect on BMI. We found that the BMI-increasing allele (minor allele) of the FTO variant was associated with increased total energy intake (effect per allele = 14.3 kcal/day [95% CI 5.9, 22.7 kcal/day], P = 6.5 × 10−4), but not with protein, carbohydrate, or fat intake. We also found that protein intake modified the association between the FTO variant and BMI (interactive effect per allele = 0.08 SD [0.03, 0.12 SD], P for interaction = 7.2 × 10−4): the association between FTO genotype and BMI was much stronger in in iduals with high protein intake (effect per allele = 0.10 SD [0.07, 0.13 SD], P = 8.2 × 10−10) than in those with low intake (effect per allele = 0.04 SD [0.01, 0.07 SD], P = 0.02). Our results suggest that the FTO variant that confers a predisposition to higher BMI is associated with higher total energy intake, and that lower dietary protein intake attenuates the association between FTO genotype and adiposity in children and adolescents.
Publisher: Springer Science and Business Media LLC
Date: 26-04-2017
DOI: 10.1038/NCOMMS14977
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study s le. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
Publisher: Springer Science and Business Media LLC
Date: 19-07-2017
DOI: 10.1038/S41467-017-00031-7
Abstract: Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass ( n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide ( p 5 × 10 −8 ) or suggestively genome wide ( p 2.3 × 10 −6 ). Replication in 63,475 (47,227 of European ancestry) in iduals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3 , IRS1 , and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN , ADAMTSL3 , and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
Publisher: Oxford University Press (OUP)
Date: 06-2019
DOI: 10.1373/CLINCHEM.2018.300335
Abstract: Associations between dairy intake and body composition and cardiometabolic traits have been inconsistently observed in epidemiological studies, and the causal relationship remains ill-defined. We performed Mendelian randomization analysis using an established genetic variant located upstream of the lactase gene (LCT-13910 C/T, rs4988235) associated with dairy intake as an instrumental variable (IV). The causal effects of dairy intake on body composition and cardiometabolic traits (lipids, glycemic traits, and inflammatory factors) were quantified by IV estimators among 182041 participants from 18 studies. Each 1 serving/day higher dairy intake was associated with higher lean mass [β (SE) = 0.117 kg (0.035) P = 0.001], higher hemoglobin A1c [0.009% (0.002) P & 0.001], lower LDL [−0.014 mmol/L (0.006) P = 0.013], total cholesterol (TC) [−0.012 mmol/L (0.005) P = 0.023], and non-HDL [−0.012 mmol/L (0.005) P = 0.028]. The LCT-13910 C/T CT + TT genotype was associated with 0.214 more dairy servings/day (SE = 0.047 P & 0.001), 0.284 cm higher waist circumference (SE = 0.118 P = 0.017), 0.112 kg higher lean mass (SE = 0.027 P = 3.8 × 10−5), 0.032 mmol/L lower LDL (SE = 0.009 P = 0.001), and 0.032 mmol/L lower TC (SE = 0.010 P = 0.001). Genetically higher dairy intake was associated with increased lean mass [0.523 kg per serving/day (0.170) P = 0.002] after correction for multiple testing (0.05/18). However, we find that genetically higher dairy intake was not associated with lipids and glycemic traits. The present study provides evidence to support a potential causal effect of higher dairy intake on increased lean mass among adults. Our findings suggest that the observational associations of dairy intake with lipids and glycemic traits may be the result of confounding.
Publisher: Public Library of Science (PLoS)
Date: 10-2015
Publisher: Elsevier BV
Date: 2019
Publisher: American Medical Association (AMA)
Date: 20-09-2019
Publisher: Springer Science and Business Media LLC
Date: 26-06-2011
DOI: 10.1038/NG.866
Publisher: Public Library of Science (PLoS)
Date: 11-2011
Publisher: Wiley
Date: 11-12-2017
Publisher: Springer Science and Business Media LLC
Date: 15-04-2021
Publisher: Public Library of Science (PLoS)
Date: 27-04-2017
Publisher: Oxford University Press (OUP)
Date: 25-04-2014
DOI: 10.1093/HMG/DDU150
Publisher: American Diabetes Association
Date: 11-09-2020
DOI: 10.2337/DB20-0070
Abstract: Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 in iduals of erse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in in iduals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10−16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
Publisher: Springer Science and Business Media LLC
Date: 07-05-2020
Publisher: Elsevier BV
Date: 11-2021
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/NCOMMS10495
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 in iduals. Twelve loci reached genome-wide significance ( P × 10 −8 ), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14 , IGF2BP1 , PLA2G6 , CRTC1 ) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/NCOMMS10494
Abstract: Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin ( LEP ) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 in iduals and followed up loci reaching P −6 in 19,979 additional in iduals. We identify five loci robustly associated ( P × 10 −8 ) with leptin levels in/near LEP , SLC32A1 , GCKR , CCNL1 and FTO . Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin , a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Publisher: BMJ
Date: 16-03-2017
DOI: 10.1136/BMJ.J1000
Publisher: Elsevier BV
Date: 07-2019
Publisher: Springer Science and Business Media LLC
Date: 02-12-2012
DOI: 10.1038/NG.2477
Publisher: Springer Science and Business Media LLC
Date: 09-2022
DOI: 10.1038/S41588-022-01165-1
Abstract: Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 in iduals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type II A muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2010
DOI: 10.1038/NG.714
Publisher: Wiley
Date: 30-10-2018
DOI: 10.1111/ADD.14438
Abstract: To use the rs1229984 variant associated with alcohol consumption as an instrument for alcohol consumption to test the causality of the association of alcohol consumption with hay fever, asthma, allergic sensitization and serum total immunoglobulin (Ig)E. Observational and Mendelian randomization analyses using genetic variants as unbiased markers of exposure to estimate causal effects, subject to certain assumptions. Europe. We included a total of 466 434 people aged 15-82 years from 17 population-based studies conducted from 1997 to 2015. The rs1229984 (ADH1B) was genotyped alcohol consumption, hay fever and asthma were self-reported. Specific and total IgE were measured from serum s les. Observational analyses showed that ever-drinking versus non-drinking, but not amount of alcohol intake, was positively associated with hay fever and inversely associated with asthma but not with allergic sensitization or serum total immunoglobulin (Ig)E. However, Mendelian randomization analyses did not suggest that the observational associations are causal. The causal odds ratio (OR) per genetically assessed unit of alcohol/week was an OR = 0.907 [95% confidence interval (CI) = 0.806, 1.019 P = 0.101] for hay fever, an OR = 0.897 (95% CI = 0.790, 1.019 P = 0.095) for asthma, an OR = 0.971 (95% CI = 0.804, 1.174 P = 0.763) for allergic sensitization and a 4.7% change (95% CI = -5.5%, 14.9% P = 0.366) for total IgE. In observational analyses, ever-drinking versus not drinking was positively associated with hay fever and negatively associated with asthma. However, the Mendelian randomization results were not consistent with these associations being causal.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1093/AJCN/NQY272
Location: United States of America
No related grants have been discovered for Tuomas Kilpeläinen.