Identification of a Novel Locus for Gait Speed Decline with Aging: The Long Life Family Study

2021 ◽  
Author(s):  
Adam J Santanasto ◽  
Mary K Wojczynski ◽  
Ryan K Cvejkus ◽  
Shiow Lin ◽  
Lihua Wang ◽  
...  
Keyword(s):  
Gait Speed ◽  
Family Study ◽  
Linkage Peak ◽  
Chromosome 16 ◽  
Association Analyses ◽  
Genome Wide ◽  
Maximum Likelihood Methods ◽  
Significant Locus ◽  
Long Life ◽  
Genetic Contributions

Abstract Background Gait speed is a powerful indicator of health with aging. Potential genetic contributions to gait speed and its decline with aging are not well defined. We determined the heritability of and potential genetic regions underlying change in gait speed using longitudinal data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64±12, range 30–110 years; 45% men). Methods Gait-speed was measured over 4 meters at baseline and follow up (7±1 years). Quantitative trait linkage analyses were completed using pedigree-based maximum-likelihood methods with logarithm of the odds (LOD) scores >3.0 indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height, and field center. Results At baseline, 26.9% of individuals had “slow” gait-speed <1.0 m/s (mean: 1.1±0.2 m/s) and gait speed declined at a rate of -0.02±0.03 m/s per year (p<0.0001). Baseline and change in gait-speed were significantly heritable (h  2 = 0.24-0.32, p<0.05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a significant locus for change in gait speed on chromosome 16p (LOD=4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Association analyses on chromosome 16 showed that the strongest variant resides within the ADCY9 gene. Conclusion Further analysis of the chromosome 16 region, and ADCY9 gene, may yield new insight on the biology of mobility decline with aging.

scholarly journals GENOME-WIDE LINKAGE ANALYSIS IDENTIFIES A NOVEL LOCUS FOR LONGITUDINAL GAIT SPEED CHANGE WITH AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S609-S610
Author(s):  
Adam J Santanasto ◽  
Mary K Wojczynski ◽  
Ryan K Cvejkus ◽  
Bharat Thyagarajan ◽  
Kaare Christensen ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Gait Speed ◽  
Linkage Peak ◽  
Likelihood Methods ◽  
Age Related ◽  
Genome Wide ◽  
Maximum Likelihood Methods ◽  
Speed Change ◽  
And Function ◽  
Genetic Contributions

Abstract Gait speed is an indicator of health and function with aging. The potential genetic contributions to gait speed and its decline with aging are not well characterized. We sought to better quantify the genetic contributions to and identify potential genes and genetic variants underlying change in gait speed among older adults. To accomplish these aims, we used data from 2379 individuals belonging to 509 families in the Long Life Family Study (mean age 64 ± 12, range 30–110 years; 45% men). Gait-speed was measured over 4 meters at baseline and after an average of 7±1.1 years. Quantitative trait linkage analyses were completed using pedigree-based maximum-likelihood methods with logarithm of the odds (LOD) scores > 3.3 indicating genome-wide significance. We also performed linkage analysis in the top 10% of families contributing to LOD scores to allow for heterogeneity among families (HLOD). Data were adjusted for age, sex, height and field center. At baseline, 26.9% of individuals had “low” gait-speed <1.0 m/s (mean: 1.1±0.2 m/s) and gait speed declined at a rate of -0.02±0.03 m/s per year (p<0.0001). Baseline and change in gait-speed were significantly heritable (h2 = 0.24-0.32, p<0.05). We did not find significant evidence for linkage for baseline gait speed; however, we identified a potentially novel locus for change in gait speed on chromosome 16p (LOD 4.2). A subset of 21 families contributed to this linkage peak (HLOD = 6.83). Sequence analysis of the chromosome 16 region may yield new insight on the biology of age-related mobility decline.

scholarly journals Genome-Wide Linkage Analysis Identifies a Novel Locus for Grip Strength: The Long Life Family Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 142-142
Author(s):  
Adam Santanasto ◽  
Mary Wojczynski ◽  
Ryan Cvejkus ◽  
Bharat Thygarajan ◽  
Kaare Christensen ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Grip Strength ◽  
Family Study ◽  
Linkage Peak ◽  
Treatment And Prevention ◽  
Quantitative Trait Linkage Analysis ◽  
Genome Wide ◽  
European Working ◽  
Maximum Likelihood Methods ◽  
Long Life

Abstract Grip strength declines with aging, is an indicator of overall health, and predicts mortality among older adults. Herein, we quantified the genetic contributions to grip strength among 4534 individuals, belonging to 574 families in the Long Life Family Study (age 70.3 ± 15.7, range 24–110 years; 56% women). Grip strength was measured using a handheld dynamometer, and the maximum value of two trials in the stronger hand was used. Quantitative trait linkage analysis was completed using pedigree-based maximum-likelihood methods with logarithm of the odds (LOD) scores >3.0 indicating genome-wide significance. Linkage analysis in the top 10% of families contributing to LOD scores was also performed to allow for heterogeneity among families (HLOD). All analyses were adjusted for age, sex, height and field center. Grip strength was lower per one year of older age (β: -0.34 ± 0.01kg, p <0.01), and overall: 24.3% of men and 19.3% of women had “low” grip strength according to European Working Group on Sarcopenia definitions. Grip strength was highly heritable (h2 = 0.37, p<0.05). We identified a potentially novel locus for grip strength on chromosome 18p (LOD 3.18) with 26 families contributing to this linkage peak (HLOD = 10.94). Deep sequencing of the chromosome 18 region may yield fundamental insight on the biology of muscle weakness with aging, and may help identify novel therapeutic targets for treatment and prevention of this common condition.

Association of fatigue, inflammation, and physical activity on gait speed: the Long Life Family Study

2021 ◽  
Author(s):  
Sharon W. Renner ◽  
Yujia Qiao ◽  
Theresa Gmelin ◽  
Adam J. Santanasto ◽  
Robert M. Boudreau ◽  
...  
Keyword(s):  
Physical Activity ◽  
Gait Speed ◽  
Family Study ◽  
Long Life

scholarly journals GWAS in 446,118 European adults identifies 78 genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

2018 ◽  
Author(s):  
Hassan S Dashti ◽  
Samuel E Jones ◽  
Andrew R Wood ◽  
Jacqueline M Lane ◽  
Vincent T. van Hees ◽  
...  
Keyword(s):  
Sleep Duration ◽  
Brain Regions ◽  
Causal Link ◽  
European Ancestry ◽  
Association Analyses ◽  
Genome Wide ◽  
Synaptic Neurotransmission ◽  
Impact Accelerometer ◽  
The Uk ◽  
Genetic Contributions

AbstractSleep is an essential homeostatically-regulated state of decreased activity and alertness conserved across animal species, and both short and long sleep duration associate with chronic disease and all-cause mortality1,2. Defining genetic contributions to sleep duration could point to regulatory mechanisms and clarify causal disease relationships. Through genome-wide association analyses in 446,118 participants of European ancestry from the UK Biobank, we discover 78 loci for self-reported sleep duration that further impact accelerometer-derived measures of sleep duration, daytime inactivity duration, sleep efficiency and number of sleep bouts in a subgroup (n=85,499) with up to 7-day accelerometry. Associations are enriched for genes expressed in several brain regions, and for pathways including striatum and subpallium development, mechanosensory response, dopamine binding, synaptic neurotransmission, catecholamine production, synaptic plasticity, and unsaturated fatty acid metabolism. Genetic correlation analysis indicates shared biological links between sleep duration and psychiatric, cognitive, anthropometric and metabolic traits and Mendelian randomization highlights a causal link of longer sleep with schizophrenia.

scholarly journals Genome-Wide Association Study of Personality Traits in the Long Life Family Study

2013 ◽  
Vol 4 ◽  
Author(s):  
Harold T. Bae ◽  
Paola Sebastiani ◽  
Jenny X. Sun ◽  
Stacy L. Andersen ◽  
E. Warwick Daw ◽  
...  
Keyword(s):  
Personality Traits ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Family Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Long Life

scholarly journals Polygenic profiles define aspects of clinical heterogeneity in ADHD

2021 ◽  
Author(s):  
Andrew Schork ◽  
Sonja LaBianca ◽  
Isabell Brickell ◽  
Dorte Helenius ◽  
Robert Loughnan ◽  
...  
Keyword(s):  
Autism Spectrum ◽  
Clinical Heterogeneity ◽  
Behavioral Traits ◽  
Complex Disorder ◽  
Novel Approach ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Significant Locus ◽  
Unique Approach ◽  
Genetic Contributions

Abstract Attention deficit hyperactivity disorder (ADHD) is a complex disorder with heterogeneous clinical presentations that manifest variability in long-term outcomes. The genetic contributions to this clinical heterogeneity, however, are not well understood. Here, we study 14 084 individuals diagnosed with ADHD to identify several genetic factors underlying clinical heterogeneity. One genome-wide significant locus was specifically associated with an autism spectrum disorder (ASD) diagnosis among individuals diagnosed with ADHD and it was not previously associated with ASD nor ADHD, individually. We used a novel approach to compare profiles of polygenic scores for groups of individuals diagnosed with ADHD and uncovered robust evidence that biology is an important factor in on-going clinical debates. Specifically, individuals diagnosed with ASD and ADHD, substance use disorder (SUD) and ADHD, or first diagnosed with ADHD in adulthood had different profiles of polygenic scores for ADHD and multiple other psychiatric, cognitive, and socio-behavioral traits. A polygene overlap between an ASD diagnosis in ADHD and cognitive performance was replicated in an independent, typically developing cohort. Our unique approach uncovered evidence of genetic heterogeneity in a widely studied complex disorder, allowing for timely contributions to the understanding of ADHD etiology and providing a model for similar studies of other disorders.

scholarly journals GENOME-WIDE ASSOCIATION STUDY OF A HEALTHY METABOLIC PHENOTYPE IN THE LONG LIFE FAMILY STUDY

2018 ◽  
Vol 2 (suppl_1) ◽  
pp. 272-272
Author(s):  
M Marron ◽  
I Miljkovic ◽  
M Wojczynski ◽  
R Boudreau ◽  
K Christensen ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Family Study ◽  
Genome Wide Association ◽  
Metabolic Phenotype ◽  
Genome Wide ◽  
Long Life

scholarly journals Polygenic profiles define aspects of clinical heterogeneity in ADHD

2021 ◽  
Author(s):  
Sonja LaBianca ◽  
Isabell Brikell ◽  
Dorte Helenius ◽  
Robert John Loughnan ◽  
Joel Mefford ◽  
...  
Keyword(s):  
Autism Spectrum ◽  
Clinical Heterogeneity ◽  
Behavioral Traits ◽  
Complex Disorder ◽  
Novel Approach ◽  
Genome Wide ◽  
Polygenic Scores ◽  
Significant Locus ◽  
Unique Approach ◽  
Genetic Contributions

Attention deficit hyperactivity disorder (ADHD) is a complex disorder with heterogeneous clinical presentations that manifest variability in long-term outcomes. The genetic contributions to this clinical heterogeneity, however, are not well understood. Here, we study 14 084 individuals diagnosed with ADHD to identify several genetic factors underlying clinical heterogeneity. One genome-wide significant locus was specifically associated with an autism spectrum disorder (ASD) diagnosis among individuals diagnosed with ADHD and it was not previously associated with ASD nor ADHD, individually. We used a novel approach to compare profiles of polygenic scores for groups of individuals diagnosed with ADHD and uncovered robust evidence that biology is an important factor in on-going clinical debates. Specifically, individuals diagnosed with ASD and ADHD, substance use disorder (SUD) and ADHD, or first diagnosed with ADHD in adulthood had different profiles of polygenic scores for ADHD and multiple other psychiatric, cognitive, and socio-behavioral traits. A polygene overlap between an ASD diagnosis in ADHD and cognitive performance was replicated in an independent, typically developing cohort. Our unique approach uncovered evidence of genetic heterogeneity in a widely studied complex disorder, allowing for timely contributions to the understanding of ADHD etiology and providing a model for similar studies of other disorders.

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