Laura Marianne Huckins, PhD
Research & Publications
Biography
News
Research Summary
The Huckins Lab focuses on understudied psychiatric disorders. In particular, we are interested in disorders affecting women, children, and vulnerable populations.
Extensive Research Description
Research Areas of Focus:
Transcriptomic Imputation
Transcriptomic Imputation approaches use eQTL reference data to create predictors of gene expression in specific tissues. These models may then be applied to genotype data to calculate predicted genetically regulated gene expression (GREX), and to test for associations between GREX and a trait of interest. These models may also be applied to summary statistics to translate GWAS data into GREX associations.
The Huckins Lab develops and applies these models; in particular, we focus on (1) improvement of statistical methodology underlying model creation; (2) probing spatio-temporal specificity of these models; (3) expansion to multi-omic prediction. We apply these models to psychiatric traits and disorders.
Disorders of Interest
The Huckins Lab focuses on understudied psychiatric disorders. In particular, we are interested in disorders affecting women, children, and vulnerable populations.
Eating Disorders
Eating Disorders are highly complex, dangerous, and understudied neuropsychiatric disorders. EDs have significant heritability (50-80%), in line with other psychiatric disorders, and have the highest mortality rates of any psychiatric disorders. Despite this, ED research receives ~$1 for every $70 spent on other major mental disorders.
EDs affect all genders, races, ethnic groups, and people of all ages. EDs may disproportionately affect members of the LGBTQIA community (16% of transgender college students report having an eating disorder, as do 3.5% of sexual minority women, and 2.1% of sexual minority men) and active duty personnel (~9% of women and ~7.5% of men have or develop an eating disorder during active duty).
The Huckins Lab is dedicated to addressing this dearth of ED research. Dr. Huckins has been involved in ED research since her PhD- including work on the first GWAS for Anorexia Nervosa, the first study of low-frequency variation, and the first study of transcriptomic imputation. Our work focuses on elucidating the tissues and systems involved in EDs, and studying multi-omic involvement, including gene expression, histone modifications, and microbiome involvement.
Post-traumatic Stress Disorder (PTSD)
Following a life-threatening traumatic exposure, about 10% of those exposed are at considerable risk for developing posttraumatic stress disorder (PTSD), a severe and disabling syndrome characterized by uncontrollable intrusive memories, nightmares, avoidance behaviours, and hyperarousal in addition to impaired cognition and negative emotion symptoms.
The Huckins Lab is interested in understanding the genetic basis of susceptibility/resilience to PTSD following trauma. A key focus of our group is understanding differing genetic aetiologies and risk factors for PTSD according to trauma type, in particular sexual assault.
Our analyses include a range of genetic, genomic, and multi-omic investigations into (1) predicting PTSD trajectory; (2) identifying shared and distinct genetic aetiologies for military and civilian PTSD; (3) identifying biological systems involved in PTSD using multi-omic imputation.
Coauthors
Research Image
Selected Publications
- Exploring the clinical and genetic associations of adult weight trajectories using electronic health records in a racially diverse biobank: a phenome-wide and polygenic risk studyXu J, Johnson JS, Signer R, Consortium E, Birgegård A, Jordan J, Kennedy MA, Landén M, Maguire SL, Martin NG, Mortensen PB, Petersen LV, Thornton LM, Bulik CM, Huckins LM. Exploring the clinical and genetic associations of adult weight trajectories using electronic health records in a racially diverse biobank: a phenome-wide and polygenic risk study. The Lancet Digital Health 2022, 4: e604-e614. PMID: 35780037, PMCID: PMC9612590, DOI: 10.1016/s2589-7500(22)00099-1.
- What next for eating disorder genetics? Replacing myths with facts to sharpen our understandingHuckins LM, Signer R, Johnson J, Wu YK, Mitchell KS, Bulik CM. What next for eating disorder genetics? Replacing myths with facts to sharpen our understanding. Molecular Psychiatry 2022, 27: 3929-3938. PMID: 35595976, PMCID: PMC9718676, DOI: 10.1038/s41380-022-01601-y.
- Predicted gene expression in ancestrally diverse populations leads to discovery of susceptibility loci for lifestyle and cardiometabolic traits.Highland HM, Wojcik GL, Graff M, Nishimura KK, Hodonsky CJ, Baldassari AR, Cote AC, Cheng I, Gignoux CR, Tao R, Li Y, Boerwinkle E, Fornage M, Haessler J, Hindorff LA, Hu Y, Justice AE, Lin BM, Lin D, Stram DO, Haiman CA, Kooperberg C, Le Marchand L, Matise TC, Kenny EE, Carlson CS, Stahl EA, Avery CL, North KE, Ambite JL, Buyske S, Loos RJ, Peters U, Young KL, Bien SA, Huckins LM. Predicted gene expression in ancestrally diverse populations leads to discovery of susceptibility loci for lifestyle and cardiometabolic traits. American Journal Of Human Genetics 2022, 109: 669-679. PMID: 35263625, PMCID: PMC9069067, DOI: 10.1016/j.ajhg.2022.02.013.
- Mapping anorexia nervosa genes to clinical phenotypes.Johnson JS, Cote AC, Dobbyn A, Sloofman LG, Xu J, Cotter L, Charney AW, Birgegård A, Jordan J, Kennedy M, Landén M, Maguire SL, Martin NG, Mortensen PB, Thornton LM, Bulik CM, Huckins LM. Mapping anorexia nervosa genes to clinical phenotypes. Psychological Medicine 2022, 1-15. PMID: 35379376, DOI: 10.1017/S0033291721004554.
- Altered gene expression and PTSD symptom dimensions in World Trade Center respondersMarchese S, Cancelmo L, Diab O, Cahn L, Aaronson C, Daskalakis NP, Schaffer J, Horn SR, Johnson JS, Schechter C, Desarnaud F, Bierer LM, Makotkine I, Flory JD, Crane M, Moline JM, Udasin IG, Harrison DJ, Roussos P, Charney DS, Koenen KC, Southwick SM, Yehuda R, Pietrzak RH, Huckins LM, Feder A. Altered gene expression and PTSD symptom dimensions in World Trade Center responders. Molecular Psychiatry 2022, 27: 2225-2246. PMID: 35177824, DOI: 10.1038/s41380-022-01457-2.
- Comparison of confound adjustment methods in the construction of gene co-expression networksCote AC, Young HE, Huckins LM. Comparison of confound adjustment methods in the construction of gene co-expression networks. Genome Biology 2022, 23: 44. PMID: 35115012, PMCID: PMC8812044, DOI: 10.1186/s13059-022-02606-0.
- Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease riskPowell SK, O’Shea C, Townsley K, Prytkova I, Dobrindt K, Elahi R, Iskhakova M, Lambert T, Valada A, Liao W, Ho SM, Slesinger PA, Huckins LM, Akbarian S, Brennand KJ. Induction of dopaminergic neurons for neuronal subtype-specific modeling of psychiatric disease risk. Molecular Psychiatry 2021, 28: 1970-1982. PMID: 34493831, PMCID: PMC8898985, DOI: 10.1038/s41380-021-01273-0.
- Massively parallel techniques for cataloguing the regulome of the human brainTownsley KG, Brennand KJ, Huckins LM. Massively parallel techniques for cataloguing the regulome of the human brain. Nature Neuroscience 2020, 23: 1509-1521. PMID: 33199899, PMCID: PMC8018778, DOI: 10.1038/s41593-020-00740-1.
- Implicit bias of encoded variables: frameworks for addressing structured bias in EHR-GWAS data.Dueñas HR, Seah C, Johnson JS, Huckins LM. Implicit bias of encoded variables: frameworks for addressing structured bias in EHR-GWAS data. Human Molecular Genetics 2020, 29: R33-R41. PMID: 32879975, PMCID: PMC7530523, DOI: 10.1093/hmg/ddaa192.
- Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts.Huckins LM, Chatzinakos C, Breen MS, Hartmann J, Klengel T, da Silva Almeida AC, Dobbyn A, Girdhar K, Hoffman GE, Klengel C, Logue MW, Lori A, Maihofer AX, Morrison FG, Nguyen HT, Park Y, Ruderfer D, Sloofman LG, van Rooij SJH, Baker DG, Chen CY, Cox N, Duncan LE, Geyer MA, Glatt SJ, Im HK, Risbrough VB, Smoller JW, Stein DJ, Yehuda R, Liberzon I, Koenen KC, Jovanovic T, Kellis M, Miller MW, Bacanu SA, Nievergelt CM, Buxbaum JD, Sklar P, Ressler KJ, Stahl EA, Daskalakis NP. Analysis of Genetically Regulated Gene Expression Identifies a Prefrontal PTSD Gene, SNRNP35, Specific to Military Cohorts. Cell Reports 2020, 31: 107716. PMID: 32492425, PMCID: PMC7359754, DOI: 10.1016/j.celrep.2020.107716.
- International Society of Psychiatric Genetics Ethics Committee: Issues facing us.Lázaro-Muñoz G, Sabatello M, Huckins L, Peay H, Degenhardt F, Meiser B, Lencz T, Soda T, Docherty A, Crepaz-Keay D, Austin J, Peterson RE, Davis LK. International Society of Psychiatric Genetics Ethics Committee: Issues facing us. American Journal Of Medical Genetics. Part B, Neuropsychiatric Genetics : The Official Publication Of The International Society Of Psychiatric Genetics 2019, 180: 543-554. PMID: 31124312, PMCID: PMC6861601, DOI: 10.1002/ajmg.b.32736.
- Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems.Zheutlin AB, Dennis J, Karlsson Linnér R, Moscati A, Restrepo N, Straub P, Ruderfer D, Castro VM, Chen CY, Ge T, Huckins LM, Charney A, Kirchner HL, Stahl EA, Chabris CF, Davis LK, Smoller JW. Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia in 106,160 Patients Across Four Health Care Systems. The American Journal Of Psychiatry 2019, 176: 846-855. PMID: 31416338, PMCID: PMC6961974, DOI: 10.1176/appi.ajp.2019.18091085.
- Synergistic effects of common schizophrenia risk variantsSchrode N, Ho SM, Yamamuro K, Dobbyn A, Huckins L, Matos MR, Cheng E, Deans PJM, Flaherty E, Barretto N, Topol A, Alganem K, Abadali S, Gregory J, Hoelzli E, Phatnani H, Singh V, Girish D, Aronow B, Mccullumsmith R, Hoffman GE, Stahl EA, Morishita H, Sklar P, Brennand KJ. Synergistic effects of common schizophrenia risk variants. Nature Genetics 2019, 51: 1475-1485. PMID: 31548722, PMCID: PMC6778520, DOI: 10.1038/s41588-019-0497-5.
- Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.Watson HJ, Yilmaz Z, Thornton LM, Hübel C, Coleman JRI, Gaspar HA, Bryois J, Hinney A, Leppä VM, Mattheisen M, Medland SE, Ripke S, Yao S, Giusti-Rodríguez P, Hanscombe KB, Purves KL, Adan RAH, Alfredsson L, Ando T, Andreassen OA, Baker JH, Berrettini WH, Boehm I, Boni C, Perica VB, Buehren K, Burghardt R, Cassina M, Cichon S, Clementi M, Cone RD, Courtet P, Crow S, Crowley JJ, Danner UN, Davis OSP, de Zwaan M, Dedoussis G, Degortes D, DeSocio JE, Dick DM, Dikeos D, Dina C, Dmitrzak-Weglarz M, Docampo E, Duncan LE, Egberts K, Ehrlich S, Escaramís G, Esko T, Estivill X, Farmer A, Favaro A, Fernández-Aranda F, Fichter MM, Fischer K, Föcker M, Foretova L, Forstner AJ, Forzan M, Franklin CS, Gallinger S, Giegling I, Giuranna J, Gonidakis F, Gorwood P, Mayora MG, Guillaume S, Guo Y, Hakonarson H, Hatzikotoulas K, Hauser J, Hebebrand J, Helder SG, Herms S, Herpertz-Dahlmann B, Herzog W, Huckins LM, Hudson JI, Imgart H, Inoko H, Janout V, Jiménez-Murcia S, Julià A, Kalsi G, Kaminská D, Kaprio J, Karhunen L, Karwautz A, Kas MJH, Kennedy JL, Keski-Rahkonen A, Kiezebrink K, Kim YR, Klareskog L, Klump KL, Knudsen GPS, La Via MC, Le Hellard S, Levitan RD, Li D, Lilenfeld L, Lin BD, Lissowska J, Luykx J, Magistretti PJ, Maj M, Mannik K, Marsal S, Marshall CR, Mattingsdal M, McDevitt S, McGuffin P, Metspalu A, Meulenbelt I, Micali N, Mitchell K, Monteleone AM, Monteleone P, Munn-Chernoff MA, Nacmias B, Navratilova M, Ntalla I, O'Toole JK, Ophoff RA, Padyukov L, Palotie A, Pantel J, Papezova H, Pinto D, Rabionet R, Raevuori A, Ramoz N, Reichborn-Kjennerud T, Ricca V, Ripatti S, Ritschel F, Roberts M, Rotondo A, Rujescu D, Rybakowski F, Santonastaso P, Scherag A, Scherer SW, Schmidt U, Schork NJ, Schosser A, Seitz J, Slachtova L, Slagboom PE, Slof-Op 't Landt MCT, Slopien A, Sorbi S, Świątkowska B, Szatkiewicz JP, Tachmazidou I, Tenconi E, Tortorella A, Tozzi F, Treasure J, Tsitsika A, Tyszkiewicz-Nwafor M, Tziouvas K, van Elburg AA, van Furth EF, Wagner G, Walton E, Widen E, Zeggini E, Zerwas S, Zipfel S, Bergen AW, Boden JM, Brandt H, Crawford S, Halmi KA, Horwood LJ, Johnson C, Kaplan AS, Kaye WH, Mitchell JE, Olsen CM, Pearson JF, Pedersen NL, Strober M, Werge T, Whiteman DC, Woodside DB, Stuber GD, Gordon S, Grove J, Henders AK, Juréus A, Kirk KM, Larsen JT, Parker R, Petersen L, Jordan J, Kennedy M, Montgomery GW, Wade TD, Birgegård A, Lichtenstein P, Norring C, Landén M, Martin NG, Mortensen PB, Sullivan PF, Breen G, Bulik CM. Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa. Nature Genetics 2019, 51: 1207-1214. PMID: 31308545, PMCID: PMC6779477, DOI: 10.1038/s41588-019-0439-2.
- Genome-wide association study implicates CHRNA2 in cannabis use disorder.Demontis D, Rajagopal VM, Thorgeirsson TE, Als TD, Grove J, Leppälä K, Gudbjartsson DF, Pallesen J, Hjorthøj C, Reginsson GW, Tyrfingsson T, Runarsdottir V, Qvist P, Christensen JH, Bybjerg-Grauholm J, Bækvad-Hansen M, Huckins LM, Stahl EA, Timmermann A, Agerbo E, Hougaard DM, Werge T, Mors O, Mortensen PB, Nordentoft M, Daly MJ, Stefansson H, Stefansson K, Nyegaard M, Børglum AD. Genome-wide association study implicates CHRNA2 in cannabis use disorder. Nature Neuroscience 2019, 22: 1066-1074. PMID: 31209380, PMCID: PMC7596896, DOI: 10.1038/s41593-019-0416-1.
- Gene expression imputation across multiple brain regions provides insights into schizophrenia riskHuckins LM, Dobbyn A, Ruderfer DM, Hoffman G, Wang W, Pardiñas AF, Rajagopal VM, Als TD, T. Nguyen H, Girdhar K, Boocock J, Roussos P, Fromer M, Kramer R, Domenici E, Gamazon ER, Purcell S, Demontis D, Børglum A, Walters J, O’Donovan M, Sullivan P, Owen M, Devlin B, Sieberts S, Cox N, Im H, Sklar P, Stahl E. Gene expression imputation across multiple brain regions provides insights into schizophrenia risk. Nature Genetics 2019, 51: 659-674. PMID: 30911161, PMCID: PMC7034316, DOI: 10.1038/s41588-019-0364-4.
- Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics.Barbeira AN, Dickinson SP, Bonazzola R, Zheng J, Wheeler HE, Torres JM, Torstenson ES, Shah KP, Garcia T, Edwards TL, Stahl EA, Huckins LM, Nicolae DL, Cox NJ, Im HK. Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics. Nature Communications 2018, 9: 1825. PMID: 29739930, PMCID: PMC5940825, DOI: 10.1038/s41467-018-03621-1.
- Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.Huckins LM, Hatzikotoulas K, Southam L, Thornton LM, Steinberg J, Aguilera-McKay F, Treasure J, Schmidt U, Gunasinghe C, Romero A, Curtis C, Rhodes D, Moens J, Kalsi G, Dempster D, Leung R, Keohane A, Burghardt R, Ehrlich S, Hebebrand J, Hinney A, Ludolph A, Walton E, Deloukas P, Hofman A, Palotie A, Palta P, van Rooij FJA, Stirrups K, Adan R, Boni C, Cone R, Dedoussis G, van Furth E, Gonidakis F, Gorwood P, Hudson J, Kaprio J, Kas M, Keski-Rahkonen A, Kiezebrink K, Knudsen GP, Slof-Op 't Landt MCT, Maj M, Monteleone AM, Monteleone P, Raevuori AH, Reichborn-Kjennerud T, Tozzi F, Tsitsika A, van Elburg A, Collier DA, Sullivan PF, Breen G, Bulik CM, Zeggini E. Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa. Molecular Psychiatry 2018, 23: 1169-1180. PMID: 29155802, PMCID: PMC5828108, DOI: 10.1038/mp.2017.88.
- Recent Genetics and Epigenetics Approaches to PTSD.Daskalakis NP, Rijal CM, King C, Huckins LM, Ressler KJ. Recent Genetics and Epigenetics Approaches to PTSD. Current Psychiatry Reports 2018, 20: 30. PMID: 29623448, PMCID: PMC6486832, DOI: 10.1007/s11920-018-0898-7.
- Linking cannabis use to depression and suicidal thoughts and behaviours.Huckins LM. Linking cannabis use to depression and suicidal thoughts and behaviours. The Lancet. Psychiatry 2017, 4: 654-656. PMID: 28750822, DOI: 10.1016/S2215-0366(17)30311-5.