Search

Your search keyword '"Keenan, Clare L."' showing total 15 results
Start Over Author "Keenan, Clare L."
15 results on '"Keenan, Clare L."'

1. Measuring autoionization decay lifetimes of optically forbidden inner valence excited states in neon atoms with attosecond noncollinear four wave mixing spectroscopy

Author

Puskar, Nicolette G., Lin, Yen-Cheng, Gaynor, James D., Schuchter, Maximilian C., Chattopadhyay, Siddhartha, Marante, Carlos, Fidler, Ashley P., Keenan, Clare L., Argenti, Luca, Neumark, Daniel M., and Leone, Stephen R.

Subjects
Physics - Atomic Physics
Abstract

Attosecond noncollinear four wave mixing spectroscopy with one attosecond extreme ultraviolet (XUV) pulse and two few-cycle near-infrared (NIR) pulses was used to measure the autoionization decay lifetimes of inner valence electronic excitations in neon atoms. After a 43-48 eV XUV photon excites a 2s electron into the 2s2p6[np] Rydberg series, broadband NIR pulses couple the 2s2p6[3p] XUV-bright state to neighboring 2s2p6[3s] and 2s2p6[3d] XUV-dark states. Controllable delays of one or both NIR pulses with respect to the attosecond XUV pulse reveal the temporal evolution of either the dark or bright states, respectively. Experimental lifetimes for the 3s, 3p, and 3d states are measured to be 7 +/- 2 fs, 48 +/- 8 fs, and 427 +/- 40 fs, respectively, with 95% confidence. Accompanying calculations with two independent ab initio theoretical methods, NewStock and ASTRA, verify the findings. The results support the expected trend that the autoionization lifetime should be longer for states that have a smaller penetration in the radial region of the 2s core hole, which in this case is for the higher angular momentum Rydberg orbitals. The underlying theory thus links the lifetime results to electron correlation and provides an assessment of the direct and exchange terms in the autoionization process., Comment: 22 pages, 5 figures, 1 table

Published
2022
Full Text
View/download PDF

2. Non-resonant Coherent Amplitude Transfer in Attosecond Four-Wave Mixing Spectroscopy

Author

Gaynor, James D., Fidler, Ashley P., Kobayashi, Yuki, Lin, Yen-Cheng, Keenan, Clare L., Neumark, Daniel M., and Leone, Stephen R.

Subjects
Physics - Atomic Physics, Quantum Physics
Abstract

Attosecond four-wave mixing spectroscopy using an XUV pulse and two noncollinear near-infrared pulses is employed to measure Rydberg wavepacket dynamics resulting from extreme ultraviolet excitation of a 3s electron in atomic argon into a series of autoionizing 3s-1np Rydberg states around 29 eV. The emitted signals from individual Rydberg states exhibit oscillatory structure and persist well beyond the expected lifetimes of the emitting Rydberg states. These results reflect substantial contributions of longer-lived Rydberg states to the four wave mixing emission signals of each individually detected state. A wavepacket decomposition analysis reveals that coherent amplitude transfer occurs predominantly from photoexcited 3s-1(n+1)p states to the observed 3s-1np Rydberg states. The experimental observations are reproduced by time-dependent Schr\"odinger equation simulations using electronic structure and transition moment calculations. The theory highlights that coherent amplitude transfer is driven non-resonantly to the 3s-1np states by the near-infrared light through 3s-1(n+1)s and 3s-1(n-1)d dark states during the four-wave mixing process.

Published
2022
Full Text
View/download PDF

3. Measuring autoionization decay lifetimes of optically forbidden inner valence excited states in neon atoms with attosecond noncollinear four-wave-mixing spectroscopy

Author

Puskar, Nicolette G, Lin, Yen-Cheng, Gaynor, James D, Schuchter, Maximilian C, Chattopadhyay, Siddhartha, Marante, Carlos, Fidler, Ashley P, Keenan, Clare L, Argenti, Luca, Neumark, Daniel M, and Leone, Stephen R

Subjects
Physical Sciences, Chemical Sciences, Atomic, Molecular and Optical Physics, Physical Chemistry, Chemical sciences, Mathematical sciences, Physical sciences
Abstract

Attosecond noncollinear four-wave-mixing spectroscopy with one attosecond extreme ultraviolet (XUV) pulse and two few-cycle near-infrared (NIR) pulses was used to measure the autoionization decay lifetimes of inner valence electronic excitations in neon atoms. After a 43-48-eV XUV photon excites a 2s electron into the 2s2p6(np) Rydberg series, broadband NIR pulses couple the 2s2p63p XUV-bright state to neighboring 2s2p63s and 2s2p63d XUV-dark states. Controllable delays of one or both NIR pulses with respect to the attosecond XUV pulse reveal the temporal evolution of either the dark or bright states, respectively. Experimental lifetimes for the 3s, 3p, and 3d states are measured to be 7±2, 48±8, and 427±40 fs, respectively, with 95% confidence. Accompanying calculations with two independent ab initio theoretical methods, newstock and astra, verify the findings. The results support the expected trend that the autoionization lifetime should be longer for states that have a smaller penetration in the radial region of the 2s core hole, which in this case is for the higher angular momentum Rydberg orbitals. The underlying theory thus links the lifetime results to electron correlation and provides an assessment of the direct and exchange terms in the autoionization process.

Published
2023

4. Nonresonant coherent amplitude transfer in attosecond four-wave-mixing spectroscopy

Author

Gaynor, James D, Fidler, Ashley P, Kobayashi, Yuki, Lin, Yen-Cheng, Keenan, Clare L, Neumark, Daniel M, and Leone, Stephen R

Subjects
Quantum Physics, Chemical Sciences, Physical Chemistry, Physical Sciences, Atomic, Molecular and Optical Physics, Chemical sciences, Mathematical sciences, Physical sciences
Abstract

Attosecond four-wave mixing (FWM) spectroscopy using an extreme ultraviolet (XUV) pulse and two noncollinear near-infrared (NIR) pulses is employed to measure Rydberg wave packet dynamics resulting from XUV excitation of a 3s electron in atomic argon into a series of autoionizing 3s-1np Rydberg states ∼29 eV. The emitted signals from individual Rydberg states exhibit oscillatory structure and persist well beyond the expected lifetimes of the emitting Rydberg states. These results reflect substantial contributions of longer-lived Rydberg states to the FWM emission signals of each individually detected state. A wave packet decomposition analysis reveals that coherent amplitude transfer occurs predominantly from photoexcited 3s-1(n+1)p states to the observed 3s-1np Rydberg states. The experimental observations are reproduced by time-dependent Schrödinger equation simulations using electronic structure and transition moment calculations. The theory highlights that coherent amplitude transfer is driven nonresonantly to the 3s-1np states by the NIR light through 3s-1(n+1)s and 3s-1(n-1)d dark states during the FWM process.

Published
2023

5. Measuring autoionization decay lifetimes of optically forbidden inner valence excited states in neon atoms with attosecond noncollinear four wave mixing spectroscopy

Author

Puskar, Nicolette G, Lin, Yen-Cheng, Gaynor, James D, Schuchter, Maximilian C, Chattopadhyay, Siddhartha, Marante, Carlos, Fidler, Ashley P, Keenan, Clare L, Argenti, Luca, Neumark, Daniel M, and Leone, Stephen R

Subjects
physics.atom-ph
Abstract

Attosecond noncollinear four wave mixing spectroscopy with one attosecondextreme ultraviolet (XUV) pulse and two few-cycle near-infrared (NIR) pulseswas used to measure the autoionization decay lifetimes of inner valenceelectronic excitations in neon atoms. After a 43-48 eV XUV photon excites a 2selectron into the 2s2p6[np] Rydberg series, broadband NIR pulses couple the2s2p6[3p] XUV-bright state to neighboring 2s2p6[3s] and 2s2p6[3d] XUV-darkstates. Controllable delays of one or both NIR pulses with respect to theattosecond XUV pulse reveal the temporal evolution of either the dark or brightstates, respectively. Experimental lifetimes for the 3s, 3p, and 3d states aremeasured to be 7 +/- 2 fs, 48 +/- 8 fs, and 427 +/- 40 fs, respectively, with95% confidence. Accompanying calculations with two independent ab initiotheoretical methods, NewStock and ASTRA, verify the findings. The resultssupport the expected trend that the autoionization lifetime should be longerfor states that have a smaller penetration in the radial region of the 2s corehole, which in this case is for the higher angular momentum Rydberg orbitals.The underlying theory thus links the lifetime results to electron correlationand provides an assessment of the direct and exchange terms in theautoionization process.

Published
2022

6. Non-resonant Coherent Amplitude Transfer in Attosecond Four-Wave Mixing Spectroscopy

Author

Gaynor, James D, Fidler, Ashley P, Kobayashi, Yuki, Lin, Yen-Cheng, Keenan, Clare L, Neumark, Daniel M, and Leone, Stephen R

Subjects
physics.atom-ph, quant-ph
Abstract

Attosecond four-wave mixing spectroscopy using an XUV pulse and twononcollinear near-infrared pulses is employed to measure Rydberg wavepacketdynamics resulting from extreme ultraviolet excitation of a 3s electron inatomic argon into a series of autoionizing 3s-1np Rydberg states around 29 eV.The emitted signals from individual Rydberg states exhibit oscillatorystructure and persist well beyond the expected lifetimes of the emittingRydberg states. These results reflect substantial contributions of longer-livedRydberg states to the four wave mixing emission signals of each individuallydetected state. A wavepacket decomposition analysis reveals that coherentamplitude transfer occurs predominantly from photoexcited 3s-1(n+1)p states tothe observed 3s-1np Rydberg states. The experimental observations arereproduced by time-dependent Schr\"odinger equation simulations usingelectronic structure and transition moment calculations. The theory highlightsthat coherent amplitude transfer is driven non-resonantly to the 3s-1np statesby the near-infrared light through 3s-1(n+1)s and 3s-1(n-1)d dark states duringthe four-wave mixing process.

Published
2022

7. Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

Author

Davis, Lea K, Yu, Dongmei, Keenan, Clare L, Gamazon, Eric R, Konkashbaev, Anuar I, Derks, Eske M, Neale, Benjamin M, Yang, Jian, Lee, S. Hong, Evans, Patrick, Barr, Cathy L, Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel Bedoya, Bienvenu, Oscar J, Bloch, Michael H, Blom, Rianne M, Bruun, Ruth D, Budman, Cathy L, Camarena, Beatriz, Campbell, Desmond, Cappi, Carolina, Cardona Silgado, Julio C, Cath, Danielle C, Cavallini, Maria C, Chavira, Denise A, Chouinard, Sylvain, Conti, David V, Cook, Edwin H, Coric, Vladimir, Cullen, Bernadette A, Deforce, Dieter, Delorme, Richard, Dion, Yves, Edlund, Christopher K, Egberts, Karin, Falkai, Peter, Fernandez, Thomas V, Gallagher, Patience J, Garrido, Helena, Geller, Daniel, Girard, Simon L, Grabe, Hans J, Grados, Marco A, Greenberg, Benjamin D, Gross-Tsur, Varda, Haddad, Stephen, Heiman, Gary A, Hemmings, Sian M. J, Hounie, Ana G, Illmann, Cornelia, Jankovic, Joseph, Jenike, Michael A, Kennedy, James L, King, Robert A, Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L, Macciardi, Fabio, McCracken, James T, McGrath, Lauren M, Mesa Restrepo, Sandra C, Moessner, Rainald, Morgan, Jubel, Muller, Heike, Murphy, Dennis L, Naarden, Allan L, Ochoa, William Cornejo, Ophoff, Roel A, Osiecki, Lisa, Pakstis, Andrew J, Pato, Michele T, Pato, Carlos N, Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L, Renner, Tobias J, Reus, Victor I, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Romero, Roxana, Rosàrio, Maria C, Rosenberg, David, Rouleau, Guy A, Ruhrmann, Stephan, Ruiz-Linares, Andres, Sampaio, Aline S, Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S, and Smit, Jan H

Subjects
Missing Heritability, Tic Disorders, Neuropsychiatric Disorders, Complex Diseases, Common Snps, Gilles, Family, Brain, Expression, Autism
Published
2013

9. Probing the predissociated levels of the S1 state of acetylene via H-atom fluorescence and photofragment fluorescence action spectroscopy.

Author

Jiang, Jun, Saladrigas, Catherine A., Erickson, Trevor J., Keenan, Clare L., and Field, Robert W.

Subjects
ACETYLENE, PREDISSOCIATION (Chemistry), HYDROGEN atom, LASER-induced fluorescence, MULTIPHOTON ionization
Abstract

We report two new experimental schemes to obtain rotationally resolved high-resolution spectra of predissociated S1 acetylene levels in the 47 000-47 300 cm−1 energy region (∼1200 cm−1 above the predissociation threshold). The two new detection schemes are compared to several other detection schemes (employed at similar laser power, molecular beam temperature, and number of signal averages) that have been used in our laboratory to study predissociated S1 acetylene levels, both in terms of the signal-to-noise ratio (S/N) of the resultant spectra and experimental simplicity. In the first method, H-atoms from the predissociated S1 acetylene levels are probed by two-photon laser-induced fluorescence (LIF). The H-atoms are pumped to the 3d level by the two-photon resonance transition at 205.14 nm. The resulting 3d–2p fluorescence (654.5 nm) is collected by a photomultiplier. The S/N of the H-atom fluorescence action spectrum is consistently better by ∼3× than that of the more widely used H-atom resonance-enhanced multiphoton ionization (REMPI) detection. Laser alignment is also considerably easier in H-atom fluorescence detection than H-atom REMPI detection due to the larger number-density of molecules that can be used in fluorescence vs. REMPI detection schemes. In the second method, fluorescence from electronically excited C2 and C2H photofragments of S1 acetylene is detected. In contrast to the H-atom detection schemes, the detected C2 and C2H photofragments are produced by the same UV laser as is used for the à – X ̃ acetylene excitation. As a result, laser alignment is greatly simplified for the photofragment fluorescence detection scheme, compared to both H-atom detection schemes. Using the photofragment fluorescence detection method, we are able to obtain action spectra of predissociated S1 acetylene levels with S/N ∼2× better than the HCCH REMPI detection and ∼10× better than H-atom and HCCH LIF detection schemes. [ABSTRACT FROM AUTHOR]

Published
2018
Full Text
View/download PDF

10. Genome-wide association study of pediatric obsessive-compulsive traits: shared genetic risk between traits and disorder

Author

Burton, Christie L., Lemire, Mathieu, Xiao, Bowei, Corfield, Elizabeth C., Erdman, Lauren, Bralten, Janita, Poelmans, Geert, Yu, Dongmei, Shaheen, S. M., Goodale, Tara, Sinopoli, Vanessa M., Askland, Kathleen D., Barlassina, Cristina, Bienvenu, O. Joseph, Black, Donald, Bloch, Michael, Brentani, Helena, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, M. Cristina, Ciullo, Valentina, Conti, David, Cook, Edwin H., Coric, Vladimir, Cullen, Bernadette A., Cusi, Danielle, Davis, Lea K., Delorme, Richard, Denys, Damiaan, Derks, Eske, Eapen, Valsamma, Edlund, Christopher, Falkai, Peter, Fyer, Abby J., Geller, Daniel A., Goes, Fernando S., Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Grünblatt, Edna, Guo, Wei, Hounie, Ana G., Jenike, Michael, Keenan, Clare L., Kennedy, James L., Khramtsova, Ekaterina A., Knowles, James A., Krasnow, Janice, Vulink, Nienke, Psychiatry, APH - Methodology, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Adult Psychiatry, ANS - Compulsivity, Impulsivity & Attention, and Complex Trait Genetics

Subjects
Obsessive-Compulsive Disorder, Adolescent, Locus (genetics), Genome-wide association study, Biology, Genetic correlation, Article, lcsh:RC321-571, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Risk Factors, Statistical significance, Human behaviour, mental disorders, Humans, Genetic risk, Child, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Biological Psychiatry, 030304 developmental biology, Genetic association, Genetics, 0303 health sciences, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Obsessive-compulsive trait, Genomics, 3. Good health, Psychiatry and Mental health, Phenotype, Trait, Compulsive Behavior, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Using a novel trait-based measure, we examined genetic variants associated with obsessive-compulsive (OC) traits and tested whether OC traits and obsessive-compulsive disorder (OCD) shared genetic risk. We conducted a genome-wide association analysis (GWAS) of OC traits using the Toronto Obsessive-Compulsive Scale (TOCS) in 5018 unrelated Caucasian children and adolescents from the community (Spit for Science sample). We tested the hypothesis that genetic variants associated with OC traits from the community would be associated with clinical OCD using a meta-analysis of all currently available OCD cases. Shared genetic risk was examined between OC traits and OCD in the respective samples using polygenic risk score and genetic correlation analyses. A locus tagged by rs7856850 in an intron of PTPRD (protein tyrosine phosphatase δ) was significantly associated with OC traits at the genome-wide significance level (p = 2.48 × 10−8). rs7856850 was also associated with OCD in a meta-analysis of OCD case/control genome-wide datasets (p = 0.0069). The direction of effect was the same as in the community sample. Polygenic risk scores from OC traits were significantly associated with OCD in case/control datasets and vice versa (p’s rg = 0.71, p = 0.062). We report the first validated genome-wide significant variant for OC traits in PTPRD, downstream of the most significant locus in a previous OCD GWAS. OC traits measured in the community sample shared genetic risk with OCD case/control status. Our results demonstrate the feasibility and power of using trait-based approaches in community samples for genetic discovery.

Published
2021

12. Partitioning the heritability of Tourette Syndrome and obsessive compulsive disorder reveals differences in genetic architecture

Author

Keller, Matthew C., Davis, Lea K., Yu, Dongmei, Keenan, Clare L., Gamazon, Eric R., Konkashbaev, Anuar I., Derks, Eske M., Neale, Benjamin M., Yang, Jian, Lee, S. Hong, Evans, Patrick, Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Berrio, Gabriel Bedoya, Bienvenu, Oscar J., Bloch, Michael H., Blom, Rianne M., Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz, Campbell, Desmond, Cappi, Carolina, Cardona Silgado, Julio C., Cath, Danielle C., Cavallini, Maria C., Chavira, Denise A., Chouinard, Sylvain, Conti, David V., Cook, Edwin H., Coric, Vladimir, Cullen, Bernadette A., Deforce, Dieter, Delorme, Richard, Dion, Yves, Edlund, Christopher K., Egberts, Karin, Falkai, Peter, Fernandez, Thomas V., Gallagher, Patience J., Garrido, Helena, Geller, Daniel, Girard, Simon L., Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Haddad, Stephen, Heiman, Gary A., Hemmings, Sian M. J., Hounie, Ana G., Illmann, Cornelia, Jankovic, Joseph, Jenike, Michael A., Kennedy, James L., King, Robert A., Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F., Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L., Macciardi, Fabio, McCracken, James T., McGrath, Lauren M., Mesa Restrepo, Sandra C., Moessner, Rainald, Morgan, Jubel, Muller, Heike, Murphy, Dennis L., Naarden, Allan L., Ochoa, William Cornejo, Ophoff, Roel A., Osiecki, Lisa, Pakstis, Andrew J., Pato, Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L., Renner, Tobias J., Reus, Victor I., Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Romero, Roxana, Rosàrio, Maria C., Rosenberg, David, Rouleau, Guy A., Ruhrmann, Stephan, Ruiz-Linares, Andres, Sampaio, Aline S., Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein, Dan J., Strengman, E., Tischfield, Jay A., Valencia Duarte, Ana V., Vallada, Homero, Van Nieuwerburgh, Filip, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Wang, Ying, Wendland, Jens R., Westenberg, Herman G. M., Shugart, Yin Yao, Miguel, Euripedes C., McMahon, William, Wagner, Michael, Nicolini, Humberto, Posthuma, Danielle, Hanna, Gregory L., Heutink, Peter, Denys, Damiaan, Arnold, Paul D., Oostra, Ben A., Nestadt, Gerald, Freimer, Nelson B., Pauls, David L., Wray, Naomi R., Stewart, S. Evelyn, Mathews, Carol A., Knowles, James A., Cox, Nancy J., and Scharf, Jeremiah M.

Subjects
Gilles, Missing Heritability, Autism, Life Sciences, Brain, Neuropsychiatric Disorders, Expression, Social and Behavioral Sciences, Tic Disorders, Common Snps, mental disorders, Medicine and Health Sciences, Complex Diseases, Family
Abstract

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

Published
2013

13. PLoS Genetics

Author

Davis, Lea K., Yu, Dongmei, Keenan, Clare L., Gamazon, Eric R., Konkashbaev, Anuar I., Derks, Eske M., and Sampaio, Aline S.

Abstract

p. 1-14 Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-04-24T14:04:29Z No. of bitstreams: 1 10.1371journal.pgen.1003864.pdf: 652592 bytes, checksum: 437d2a27dc80379e2b90d7ee691207ec (MD5) Approved for entry into archive by Rodrigo Meirelles (rodrigomei@ufba.br) on 2014-10-10T15:05:44Z (GMT) No. of bitstreams: 1 10.1371journal.pgen.1003864.pdf: 652592 bytes, checksum: 437d2a27dc80379e2b90d7ee691207ec (MD5) Made available in DSpace on 2014-10-10T15:05:44Z (GMT). No. of bitstreams: 1 10.1371journal.pgen.1003864.pdf: 652592 bytes, checksum: 437d2a27dc80379e2b90d7ee691207ec (MD5) Previous issue date: 2013 The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.

Published
2013
Full Text
View/download PDF

14. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture

Author

Patrick Evans, Jay A. Tischfield, Anuar Konkashbaev, Richard Delorme, Sandra Catalina Mesa Restrepo, Margaret A. Richter, Gregory L. Hanna, Allan L. Naarden, Michele T. Pato, Jian Yang, Denise A. Chavira, Damiaan Denys, Paul Sandor, Michael A. Jenike, Sian M. J. Hemmings, Paul D. Arnold, Stephan Ruhrmann, H.G.M. Westenberg, Yves Dion, Cathy L. Barr, Andres Ruiz-Linares, Brooke Sheppard, Leonhard Lennertz, Eske M. Derks, Lauren M. McGrath, Barbara Kremeyer, Marion Leboyer, Victor I. Reus, Cornelia Illmann, S. Evelyn Stewart, Dan J. Stein, Ana Gabriela Hounie, James T. McCracken, R. Kurlan, Chunyu Liu, Aline S. Sampaio, Thomas L. Lowe, Benjamin M. Neale, Yehuda Pollak, Desmond Campbell, Fabio Macciardi, Mary M. Robertson, Benjamin D. Greenberg, Ben A. Oostra, Rainald Moessner, Gary A. Heiman, Nuria Lanzagorta, Sylvain Chouinard, Rianne M. Blom, Karin Egberts, Carlos N. Pato, David V. Conti, Carol A. Mathews, Ying Wang, Marco A. Grados, Julio C. Cardona Silgado, S. Hong Lee, H. Müller, Eric R. Gamazon, Humberto Nicolini, Jan Smit, Euripedes Constantino Miguel, Jens R. Wendland, Cathy L. Budman, Laura Bellodi, Danielle Posthuma, Jubel Morgan, David R. Rosenberg, John Piacentini, Hans J. Grabe, Mark A. Riddle, Beatriz Camarena, Naomi R. Wray, Eric Strengman, Dennis L. Murphy, Simon Girard, Christine Lochner, Ruth D. Bruun, Joseph Jankovic, Edwin H. Cook, William M. McMahon, Scott L. Rauch, James F. Leckman, Peter Falkai, Fortu Benarroch, Christopher K. Edlund, Gabriel Bedoya Berrío, Homero Vallada, Susanne Walitza, Nelson B. Freimer, Stephen A. Haddad, Yin Yao Shugart, Danielle C. Cath, Nancy J. Cox, Varda Gross-Tsur, Guy A. Rouleau, Bernadette Cullen, Michael H. Bloch, Dieter Deforce, David L. Pauls, Thomas V. Fernandez, Roel A. Ophoff, Filip Van Nieuwerburgh, Gerald Nestadt, Dongmei Yu, Helena Garrido, Robert A. King, James L. Kennedy, Clare L. Keenan, Lisa Osiecki, Jack Samuels, Jeremy Veenstra-VanderWeele, Ana V. Valencia Duarte, James A. Knowles, Patience J. Gallagher, Carolina Cappi, Maria Conceição do Rosário, Andrew J. Pakstis, Christopher Pittenger, Michael Wagner, Jeremiah M. Scharf, Daniel A. Geller, Vladimir Coric, Tobias J. Renner, Oscar J. Bienvenu, Roxana Romero, William Cornejo Ochoa, Peter Heutink, Lea K. Davis, Harvey S. Singer, Maria Cristina Cavallini, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, Department of Psychiatry and Mental Health, Faculty of Health Sciences, Univ Chicago, Harvard Univ, Broad Inst Harvard & MIT, Univ Amsterdam, Massachusetts Gen Hosp, Univ Queensland, Univ Hlth Network, Hosp Sick Children, Univ Vita Salute San Raffaele, Hadassah Hebrew Univ Med Ctr, Univ Pontificia Bolivariana, Johns Hopkins Univ, Yale Univ, North Shore Long Isl Jewish Med Ctr, NYU Med Ctr, North Shore Long Isl Jewish Hlth Syst, Hofstra Univ, Inst Nacl Psiquiatria Ramon de la Fuente Muniz, UCL, Univ Hong Kong, Universidade de São Paulo (USP), Vrije Univ Amsterdam, Univ Utrecht, Altrecht Acad Anxiety Ctr, Univ Milan, Univ Calif Los Angeles, Univ Calif San Diego, Univ Montreal, Univ Illinois, Univ Ghent, Inst Pasteur, French Natl Sci Fdn, Hop Robert Debre, Univ Wurzburg, Univ Munich, Univ Med Greifswald, Butler Hosp, Shaare Zedek Med Ctr, Rutgers State Univ, Univ Stellenbosch, Baylor Coll Med, Ctr Addict & Mental Hlth, Univ Toronto, Overlook Hosp, Carracci Med Grp, Inst Mondor Rech Biomed, Univ Bonn, Univ Calif San Francisco, UCI, Univ Utah, NIMH Intramural Res Program, Med City Dallas Hosp, Univ Med Ctr, Univ So Calif, Partners Psychiat & McLean Hosp, Sunnybrook Hlth Sci Ctr, St George Hosp, Sch Med, Hosp Nacl Ninos Dr Carlos Saenz Herrera, Universidade Federal de São Paulo (UNIFESP), Wayne State Univ, Detroit Med Ctr, McGill Univ, Univ Cologne, Universidade Federal da Bahia (UFBA), Youthdale Treatment Ctr, Johns Hopkins Univ Sch Med, Univ Cape Town, Univ Med Ctr Utrecht, Vanderbilt Univ, Univ Zurich, Inst Royal Netherlands Acad Arts & Sci NIN KNAW, Natl Inst Genom Med SAP, Vrije Univ Amsterdam Med Ctr, Erasmus Univ, Univ Michigan, German Ctr Neurodegenerat Dis, Erasmus MC, Univ British Columbia, Brigham & Womens Hosp, Davis, Lk, Yu, D, Keenan, Cl, Gamazon, Er, Konkashbaev, Ai, Derks, Em, Neale, Bm, Yang, J, Lee, Sh, Evans, P, Barr, Cl, Bellodi, Laura, Benarroch, F, Berrio, Gb, Bienvenu, Oj, Bloch, Mh, Blom, Rm, Bruun, Rd, Budman, Cl, Camarena, B, Campbell, D, Cappi, C, Cardona Silgado, Jc, Cath, Dc, Cavallini, Mc, Chavira, Da, Chouinard, S, Conti, Dv, Cook, Eh, Coric, V, Cullen, Ba, Deforce, D, Delorme, R, Dion, Y, Edlund, Ck, Egberts, K, Falkai, P, Fernandez, Tv, Gallagher, Pj, Garrido, H, Geller, D, Girard, Sl, Grabe, Hj, Grados, Ma, Greenberg, Bd, Gross Tsur, V, Haddad, S, Heiman, Ga, Hemmings, Sm, Hounie, Ag, Illmann, C, Jankovic, J, Jenike, Ma, Kennedy, Jl, King, Ra, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, Jf, Lennertz, L, Liu, C, Lochner, C, Lowe, Tl, Macciardi, F, Mccracken, Jt, Mcgrath, Lm, Mesa Restrepo, Sc, Moessner, R, Morgan, J, Muller, H, Murphy, Dl, Naarden, Al, Ochoa, Wc, Ophoff, Ra, Osiecki, L, Pakstis, Aj, Pato, Mt, Pato, Cn, Piacentini, J, Pittenger, C, Pollak, Y, Rauch, Sl, Renner, Tj, Reus, Vi, Richter, Ma, Riddle, Ma, Robertson, Mm, Romero, R, Rosàrio, Mc, Rosenberg, D, Rouleau, Ga, Ruhrmann, S, Ruiz Linares, A, Sampaio, A, Samuels, J, Sandor, P, Sheppard, B, Singer, H, Smit, Jh, Stein, Dj, Strengman, E, Tischfield, Ja, Valencia Duarte, Av, Vallada, H, Van Nieuwerburgh, F, Veenstra Vanderweele, J, Walitza, S, Wang, Y, Wendland, Jr, Westenberg, Hg, Shugart, Yy, Miguel, Ec, Mcmahon, W, Wagner, M, Nicolini, H, Posthuma, D, Hanna, Gl, Heutink, P, Denys, D, Arnold, Pd, Oostra, Ba, Nestadt, G, Freimer, Nb, Pauls, Dl, Wray, Nr, Stewart, Se, Mathews, Ca, Knowles, Ja, Cox, Nj, Scharf, Jm, Functional Genomics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Davis, Lea K, Yu, Dongmei, Keenan, Clare L, Gamazon, Eric R, Lee, S Hong, Scharf, Jeremiah M, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Other departments, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Adult Psychiatry, and Graduate School

Subjects
Cancer Research, Obsessive-Compulsive Disorder, COMPLEX DISEASES, Genome-wide association study, heritability, Genome-wide association studies, neurobehavioral disorders, COMMON SNPS, 0302 clinical medicine, Gene Frequency, Missing heritability problem, MISSING HERITABILITY, Cerebellum, Heritability of autism, BRAIN, Genetics (clinical), Genetics, ddc:616, Genetics & Heredity, 0303 health sciences, Chromosome 15, humanities, FAMILY, obsessive-compulsive disorder, genetics [Tourette Syndrome], Phenotype, NEUROPSYCHIATRIC DISORDERS, GENÔMICA, Research Article, EXPRESSION, lcsh:QH426-470, SNP, Biology, Quantitative trait locus, Genome-wide Complex Trait Analysis, Genetic correlation, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Chromosomes, TIC DISORDERS, 03 medical and health sciences, Quantitative Trait, Heritable, mental disorders, genetic risk factors, Humans, ddc:610, AUTISM, Variant genotypes, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, genetics [Obsessive-Compulsive Disorder], Tourette syndrome, Parietal lobe, Biology and Life Sciences, Heritability, Genetic architecture, Minor allele frequency, Trastorno Obsesivo Compulsivo, lcsh:Genetics, pathology [Obsessive-Compulsive Disorder], genetic variation, pathology [Tourette Syndrome], Síndrome de Tourette, 030217 neurology & neurosurgery, GILLES, Genome-Wide Association Study, Tourette Syndrome
Abstract

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures., Author Summary Family and twin studies have shown that genetic risk factors are important in the development of Tourette Syndrome (TS) and obsessive compulsive disorder (OCD). However, efforts to identify the individual genetic risk factors involved in these two neuropsychiatric disorders have been largely unsuccessful. One possible explanation for this is that many genetic variations scattered throughout the genome each contribute a small amount to the overall risk. For TS and OCD, the genetic architecture (characterized by the number, frequency, and distribution of genetic risk factors) is presently unknown. This study examined the genetic architecture of TS and OCD in a variety of ways. We found that rare genetic changes account for more genetic risk in TS than in OCD; certain chromosomes contribute to OCD risk more than others; and variants that influence the level of genes expressed in two regions of the brain can account for a significant amount of risk for both TS and OCD. Results from this study might help in determining where, and what kind of variants are individual risk factors for TS and OCD and where they might be located in the human genome.

Published
2013

15. Probing the predissociated levels of the S 1 state of acetylene via H-atom fluorescence and photofragment fluorescence action spectroscopy.

Author

Jiang J, Saladrigas CA, Erickson TJ, Keenan CL, and Field RW

Abstract

We report two new experimental schemes to obtain rotationally resolved high-resolution spectra of predissociated S 1 acetylene levels in the 47 000-47 300 cm -1 energy region (∼1200 cm -1 above the predissociation threshold). The two new detection schemes are compared to several other detection schemes (employed at similar laser power, molecular beam temperature, and number of signal averages) that have been used in our laboratory to study predissociated S 1 acetylene levels, both in terms of the signal-to-noise ratio (S/N) of the resultant spectra and experimental simplicity. In the first method, H-atoms from the predissociated S 1 acetylene levels are probed by two-photon laser-induced fluorescence (LIF). The H-atoms are pumped to the 3 d level by the two-photon resonance transition at 205.14 nm. The resulting 3 d -2 p fluorescence (654.5 nm) is collected by a photomultiplier. The S/N of the H-atom fluorescence action spectrum is consistently better by ∼3× than that of the more widely used H-atom resonance-enhanced multiphoton ionization (REMPI) detection. Laser alignment is also considerably easier in H-atom fluorescence detection than H-atom REMPI detection due to the larger number-density of molecules that can be used in fluorescence vs . REMPI detection schemes. In the second method, fluorescence from electronically excited C 2 and C 2 H photofragments of S 1 acetylene is detected. In contrast to the H-atom detection schemes, the detected C 2 and C 2 H photofragments are produced by the same UV laser as is used for the à - X ̃ acetylene excitation. As a result, laser alignment is greatly simplified for the photofragment fluorescence detection scheme, compared to both H-atom detection schemes. Using the photofragment fluorescence detection method, we are able to obtain action spectra of predissociated S 1 acetylene levels with S/N ∼2× better than the HCCH REMPI detection and ∼10× better than H-atom and HCCH LIF detection schemes.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results