Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss.

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss.

Gap detection responses modelled using the Hill equation in adults with well-controlled HIV.

OBJECTIVE: This study's objective was determining whether gap detection deficits are present in a longstanding cohort of people living with HIV (PLWH) compared to those living without HIV (PLWOH) using a new gap detection modelling technique (i.e. fitting gap responses using the Hill equation and analysing the individual gap detection resulting curves with non-linear statistics). This approach provides a measure of both gap threshold and the steepness of the gap length/correct detection relationship. DESIGN: The relationship between the correct identification rate at each gap length was modelled using the Hill equation. Results were analysed using a nonlinear mixed-effect regression model. STUDY SAMPLE: 45 PLWH (age range 41-78) and 39 PLWOH (age range 38-79) were enrolled and completed gap detection testing. RESULTS: The likelihood ratio statistic comparing the full regression model with the HIV effects to the null model, assuming one population curve for both groups, was highly significant (p < 0.001), suggesting a less precise relationship between gap length and correct detection in PLWH. CONCLUSIONS: PLWH showed degraded gap detection ability compared to PLWOH, likely due to central nervous system effects of HIV infection or treatment. The Hill equation provided a new approach for modelling gap detection ability.

Prenatal Exposure to Tobacco and Alcohol Alters Development of the Neonatal Auditory System.

Prenatal exposures to alcohol (PAE) and tobacco (PTE) are known to produce adverse neonatal and childhood outcomes including damage to the developing auditory system. Knowledge of the timing, extent, and combinations of these exposures on effects on the developing system is limited. As part of the physiological measurements from the Safe Passage Study, Auditory Brainstem Responses (ABRs) and Transient Otoacoustic Emissions (TEOAEs) were acquired on infants at birth and one-month of age. Research sites were in South Africa and the Northern Plains of the U.S. Prenatal information on alcohol and tobacco exposure was gathered prospectively on mother/infant dyads. Cluster analysis was used to characterize three levels of PAE and three levels of PTE. Repeated-measures ANOVAs were conducted for newborn and one-month-old infants for ABR peak latencies and amplitudes and TEOAE levels and signal-to-noise ratios. Analyses controlled for hours of life at test, gestational age at birth, sex, site, and other exposure. Significant main effects of PTE included reduced newborn ABR latencies from both ears. PTE also resulted in a significant reduction of ABR peak amplitudes elicited in infants at 1-month of age. PAE led to a reduction of TEOAE amplitude for 1-month-old infants but only in the left ear. Results indicate that PAE and PTE lead to early disruption of peripheral, brainstem, and cortical development and neuronal pathways of the auditory system, including the olivocochlear pathway.

Birth Prevalence of Congenital Cytomegalovirus Infection in HIV-Exposed Uninfected Children in the Era of Combination Antiretroviral Therapy.

OBJECTIVES: To estimate birth prevalence of congenital cytomegalovirus (cCMV) in HIV-exposed uninfected children born in the current era of combination antiretroviral therapy and describe cCMV-related neurodevelopmental and hearing outcomes. STUDY DESIGN: The Surveillance Monitoring for ART Toxicities cohort study follows HIV-exposed uninfected children at 22 sites in the US and Puerto Rico. Birth cCMV prevalence was estimated in a subset of participants who had blood pellets collected within three weeks of birth and underwent ≥1 of 6 assessments evaluating cognitive and language development including an audiologic examination between 1 and 5 years of age. Detection of CMV DNA by polymerase chain reaction testing of peripheral blood mononuclear cells was used to diagnose cCMV. Proportions of suboptimal assessment scores were compared by cCMV status using Fisher exact test. RESULTS: Mothers of 895 eligible HIV-exposed uninfected children delivered between 2007 and 2015. Most (90%) were on combination antiretroviral therapy, 88% had an HIV viral load of ≤400 copies/mL, and 93% had CD4 cell counts of ≥200 cells/µL. Eight infants were diagnosed with cCMV, yielding an estimated prevalence of 0.89% (95% CI, 0.39%-1.75%). After adjusting for a sensitivity of 70%-75% for the testing method, projected prevalence was 1.2%-1.3%. No differences were observed in cognitive, language and hearing assessments by cCMV status. CONCLUSIONS: Although birth cCMV prevalence in HIV-exposed uninfected children born to women with well-controlled HIV is trending down compared with earlier combination antiretroviral therapy-era estimates, it is above the 0.4% reported for the general US population. HIV-exposed uninfected children remain at increased risk for cCMV.

Chronic Cigarette Smoking Associates Directly and Indirectly with Self-Reported Olfactory Alterations: Analysis of the 2011-2014 National Health and Nutrition Examination Survey.

INTRODUCTION: Population-based studies show inconsistent effects of cigarette smoking on olfactory function. We aimed to identify direct and indirect associations between measures of smoking exposure/nicotine dependence and altered olfaction in a nationally representative sample of adults. METHODS: NHANES 2011-2014 (n = 7418) participants (mean age = 57.8 ± 12.2 years) self-reported olfaction and related health and demographic risks. Affirmative answers to three questions defined altered olfaction (olfactory problems in the past years; worse ability since age 25; phantom smells). Smoking (never, former, current) was self-reported by chronicity (pack years, PY) and dependency (time to first cigarette upon waking) and verified by serum cotinine. Associations were tested with logistic regression, reporting odds ratios (ORs) and 95% confidence intervals (CIs), and mediation models. RESULTS: Estimated prevalence of altered olfaction was 22.3%, with age-related increases. Nearly half of the sample were former/current smokers (47.4%). Controlling for olfactory-related risks, ≥10 PY smokers had significantly greater odds of altered olfaction versus never smokers (OR 1.36, CI: 1.06-1.74). The odds of altered olfaction were heightened among current smokers (≥10 PY) who also had high nicotine dependence (smoked ≤30 min of waking) (OR 1.41, CI: 1.01-1.99). Light smokers (≤10 PY smokers) did not show increased odds versus never smokers. Current smokers who also were heavy drinkers (≥4 drinks/day) had the highest odds for altered olfaction (OR 1.96, CI: 1.20-3.19). Olfactory-related pathologies (sinonasal problems, serious head injury, tonsillectomy, xerostomia) partially mediated the association between smoking and altered olfaction. CONCLUSIONS: Chronic cigarette smoking was associated with increased odds of self-reported olfactory alterations, directly and indirectly via olfactory-related pathologies. IMPLICATIONS: Analysis of the US nationally representative data revealed significant positive associations between chronic smoking and alterations in the sense of smell. Rates of smell alteration (self-reported problems in the past year, losses with aging, and phantom smells) increased from 23% among adults to 33% for chronic smokers and 38% for chronic smokers who also reported heavy drinking. Chronic smoking showed associations with smell alteration that were direct and indirect through exposure to olfactory-related pathologies (naso-sinus problems, dry mouth, head/facial injury). Smell alteration can impact smokers' quality of life by challenging the ability to sense warning odors, food flavor, and olfactory-stimulated emotions and memories.

Vital Signs: Noise-Induced Hearing Loss Among Adults - United States 2011-2012.

INTRODUCTION: The 2016 National Academies of Sciences report "Hearing Health Care for Adults: Priorities for Improving Access and Affordability" included a call to action for government agencies to strengthen efforts to collect, analyze, and disseminate population-based data on hearing loss in adults. METHODS: CDC analyzed the most recent available data collected both by questionnaire and audiometric tests of adult participants aged 20-69 years in the 2011-2012 National Health and Nutrition Examination Survey (NHANES) to determine the presence of audiometric notches indicative of noise-induced hearing loss. Prevalence of both unilateral and bilateral audiometric notches and their association with sociodemographics and self-reported exposure to loud noise were calculated. RESULTS: Nearly one in four adults (24%) had audiometric notches, suggesting a high prevalence of noise-induced hearing loss. The prevalence of notches was higher among males. Almost one in four U.S. adults who reported excellent or good hearing had audiometric notches (5.5% bilateral and 18.0% unilateral). Among participants who reported exposure to loud noise at work, almost one third had a notch. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Noise-induced hearing loss is a significant, often unrecognized health problem among U.S. adults. Discussions between patients and personal health care providers about hearing loss symptoms, tests, and ways to protect hearing might help with early diagnosis of hearing loss and provide opportunities to prevent harmful noise exposures. Avoiding prolonged exposure to loud environments and using personal hearing protection devices can prevent noise-induced hearing loss.

Epidemiology of Dizziness and Balance Problems in Children in the United States: A Population-Based Study.

OBJECTIVE: To study national prevalence of dizziness and balance problems in US children and explore associated risk factors and patterns of healthcare utilization. STUDY DESIGN: A multistage, nationally representative, probability sample of children (n = 10,954; aged 3-17 years) was examined based on the 2012 National Health Interview Survey Child Balance Supplement. Parents were asked if during the past year their child was bothered by symptoms of dizziness and balance problems: vertigo (motion sensation), light-headedness/fainting, clumsiness/poor coordination, poor balance/unsteadiness when standing-up or walking, frequent falls, or other dizziness and balance problems. Logistic regression was used to examine associations with sociodemographic information, birth weight, developmental delays, and significant health conditions. RESULTS: Prevalence of dizziness and balance problems was 5.3% (3.3 million US children); females, 5.7%, males, 5.0%. Non-Hispanic white (6.1%) had increased prevalence compared with Hispanic (4.6%) and non-Hispanic black (4.3%) children, P = .01. Prevalence increased with age, from 4.1% for children aged 3-5 years to 7.5% for children aged 15-17 years, P < .001. Even though the majority had symptoms rated as "no problem" or "a small problem," 18.6% (600,000 US children) had symptoms rated as "moderate," "big," or "very big" problems. Overall, 36.0% of children with dizziness and balance problems were seen by healthcare professionals during the past year and 29.9% received treatment. Among children with dizziness and balance problems rated as moderate/big/very big problems, 71.6% had seen healthcare professionals and 62.4% received treatment for dizziness and balance problems. CONCLUSIONS: The risk factors identified provide useful epidemiologic information about dizziness and balance problems in children and will be used in tracking the Healthy People 2020 goal to increase utilization of healthcare services for these children.

Vestibular vertigo and comorbid cognitive and psychiatric impairment: the 2008 National Health Interview Survey.

BACKGROUND/AIMS: Patients with vestibular disease have been observed to have concomitant cognitive and psychiatric dysfunction. We evaluated the association between vestibular vertigo, cognitive impairment and psychiatric conditions in a nationally representative sample of US adults. METHODS: We performed a cross-sectional analysis using the 2008 National Health Interview Survey (NHIS), which included a Balance and Dizziness Supplement, and questions about cognitive function and psychiatric comorbidity. We evaluated the association between vestibular vertigo, cognitive impairment (memory loss, difficulty concentrating, confusion) and psychiatric diagnoses (depression, anxiety and panic disorder). RESULTS: We observed an 8.4% 1-year prevalence of vestibular vertigo among US adults. In adjusted analyses, individuals with vestibular vertigo had an eightfold increased odds of 'serious difficulty concentrating or remembering' (OR 8.3, 95% CI 4.8 to 14.6) and a fourfold increased odds of activity limitation due to difficulty remembering or confusion (OR 3.9, 95% CI 3.1 to 5.0) relative to the rest of the US adults. Individuals with vestibular vertigo also had a threefold increased odds of depression (OR 3.4, 95% CI 2.9 to 3.9), anxiety (OR 3.2, 95% CI 2.8 to 3.6) and panic disorder (OR 3.4, 95% CI 2.9 to 4.0). CONCLUSIONS: Our findings indicate that vestibular impairment is associated with increased risk of cognitive and psychiatric comorbidity. The vestibular system is anatomically connected with widespread regions of the cerebral cortex, hippocampus and amygdala. Loss of vestibular inputs may lead to impairment of these cognitive and affective circuits. Further longitudinal research is required to determine if these associations are causal.

New chemosensory component in the U.S. National Health and Nutrition Examination Survey (NHANES): first-year results for measured olfactory dysfunction.

The U.S. NHANES included chemosensory assessments in the 2011-2014 protocol. We provide an overview of this protocol and 2012 olfactory exam findings. Of the 1818 NHANES participants aged ≥40 years, 1281 (70.5 %) completed the exam; non-participation mostly was due to time constraints. Health technicians administered an 8-item, forced-choice, odor identification task scored as normosmic (6-8 odors identified correctly) versus olfactory dysfunction, including hyposmic (4-5 correct) and anosmic/severe hyposmic (0-3 correct). Interviewers recorded self-reported smell alterations (during past year, since age 25, phantosmia), histories of sinonasal problems, xerostomia, dental extractions, head or facial trauma, and chemosensory-related treatment and changes in quality of life. Olfactory dysfunction was found in 12.4 % (13.3 million adults; 55 % males/45 % females) including 3.2 % anosmic/severe hyposmic (3.4 million; 74 % males/26 % females). Selected age-specific prevalences were 4.2 % (40-49 years), 12.7 % (60-69 years), and 39.4 % (80+ years). Among adults ≥70 years, misidentification rates for warning odors were 20.3 % for smoke and 31.3 % for natural gas. The highest sensitivity (correctly identifying dysfunction) and specificity (correctly identifying normosmia) of self-reported olfactory alteration was among anosmics/severe hyposmics (54.4 % and 78.1 %, respectively). In age- and sex-adjusted logistic regression analysis, risk factors of olfactory dysfunction were racial/ethnic minority, income-to-poverty ratio ≤ 1.1, education

Prevalence and Risk Factors of Self-Reported Smell and Taste Alterations: Results from the 2011-2012 US National Health and Nutrition Examination Survey (NHANES).

Chemosensory problems challenge health through diminished ability to detect warning odors, consume a healthy diet, and maintain quality of life. We examined the prevalence and associated risk factors of self-reported chemosensory alterations in 3603 community-dwelling adults (aged 40+ years), from the nationally representative, US National Health and Nutrition Examination Survey (NHANES) 2011-2012. In this new NHANES component, technicians surveyed adults in the home about perceived smell and taste problems, distortions, and diminished abilities since age 25 (termed "alterations"), and chemosensory-related health risks and behaviors. The prevalence of self-reported smell alteration was 23%, including phantosmia at 6%; taste was 19%, including dysgeusia at 5%. Prevalence rates increased progressively with age, highest in those aged 80+ years (smell, 32%; taste, 27%). In multivariable logistic regression, controlling for sociodemographics, health behaviors, and chemosensory-related conditions, the strongest independent risk factor for smell alteration was sinonasal symptoms (odds ratio [OR] = 2.06; 95% confidence interval [CI]: 1.63-2.61), followed by heavy drinking, loss of consciousness from head injury, family income ≤110% poverty threshold, and xerostomia. For taste, the strongest risk factor was xerostomia (OR = 2.65; 95% CI: 1.97-3.56), followed by nose/facial injury, lower educational attainment, and fair/poor health. Self-reported chemosensory alterations are prevalent in US adults, supporting increased attention to decreasing their modifiable risks, managing safety/health consequences, and expanding chemosensory screening/testing and treatments.

Childhood otitis media is associated with dizziness in adulthood: the HUNT cohort study.

The objective of the study was to examine the association between otitis media in childhood and dizziness in adulthood. Longitudinal, population-based cohort study of 21,962 adults (aged 20-59 years, mean 40) who completed a health questionnaire in the Nord-Trøndelag Hearing Loss Study was conducted. At 7, 10 and 13 years of age, the same individuals underwent screening audiometry in a longitudinal school hearing investigation. Children found with hearing loss underwent an ear, nose and throat specialist examination. Adults diagnosed with childhood chronic suppurative otitis media (n = 102) and childhood hearing loss after recurrent acute otitis media (n = 590) were significantly more likely to have increased risk of reported dizziness when compared to adults with normal hearing as children at the school investigation and also a negative history of recurrent otitis media (n = 21,270), p < 0.05. After adjusting for adult age, sex and socio-economic status, the odds ratios were 2.1 [95 % confidence interval (CI): 1.4-3.3] and 1.3 (95 % CI: 1.0-1.5), respectively. This longitudinal cohort study suggests that childhood chronic suppurative otitis media and childhood hearing loss after recurrent acute otitis media are associated with increased risk of dizziness in adulthood. This might reflect a permanent effect of inflammatory mediators or toxins on the vestibular system. The new finding stresses the importance of treatment and prevention of these otitis media conditions.

Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study.

OBJECTIVE: We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. DESIGN: Population-based cohort study. STUDY SAMPLE: A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. RESULTS: Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. CONCLUSIONS: Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women.

The safe passage study: design, methods, recruitment, and follow-up approach.

BACKGROUND: The Safe Passage Study is a large, prospective, multidisciplinary study designed to (1) investigate the association between prenatal alcohol exposure, sudden infant death syndrome (SIDS), and stillbirth, and (2) determine the biological basis of the spectrum of phenotypic outcomes from exposure, as modified by environmental and genetic factors that increase the risk of stillbirth, SIDS, and in surviving children, fetal alcohol spectrum disorders. METHODS: The results provided are based on an interim assessment of 6004 women enrolled, out of the 12,000 projected, from the Northern Plains, US, and Cape Town, South Africa, areas known to be of high risk for maternal drinking during pregnancy. Research objectives, study design, and descriptive statistics, including consent, recruitment, and retention information, are provided. RESULTS: Overall visit compliance is 87%, and includes prenatal, delivery/newborn, and postnatal contacts through 1 year post-delivery. Pregnancy outcome ascertainment is 98% prior to medical chart review; less than 2% of women withdraw. Consent for the use of DNA and placental tissue exceed 94%, and consent to participate in the autopsy portion of the study is 71%. CONCLUSIONS: The Safe Passage Study is the first multi-site study of SIDS and stillbirth to integrate prospectively collected exposure information with multidisciplinary biological information in the same maternal and fetal/infant dyad using a common protocol. Essential components of the study design and its success are close ties to the community and rigorous systems and processes to ensure compliance with the study protocol and procedures.

Cochlear function among HIV-seropositive and HIV-seronegative men and women.

OBJECTIVES: There is limited research about cochlear function in adults who are human immunodeficiency virus (HIV) positive (+). The aim of the present study was to collect measures of cochlear function in a large sample of adults with, or at risk for, HIV infection, to evaluate associations between HIV status, HIV treatment, and cochlear function. DESIGN: Distortion product otoacoustic emissions (DPOAEs) were used to evaluate cochlear function in 506 participants; 329 men, 150 of whom were HIV+, and 177 women, 136 of whom were HIV+. DPOAEs were measured at frequencies 1000, 2000, 3000, 4000, and 6000 Hz. A DPOAE nonresponse (NR) was defined as an absolute DPOAE level less than -15 dB SPL or a difference between the absolute DPOAE level and the background noise level less than 6 dB. The total number of NRs was calculated for each ear. The associations of demographic variables, HIV status, and HIV treatment with number of NRs were evaluated with univariate and multivariate ordinal regression models. RESULTS: There was a statistically significant increase in the odds of higher numbers of NRs with age, being male, and being non-Black, but not with HIV status. Among HIV+ participants, there were no statistically significant associations of the HIV disease status or treatment variables with higher number of NRs. CONCLUSION: The authors found no evidence of impaired cochlear function by HIV disease status or highly active antiretroviral therapy-treated HIV infection in this cross-sectional study.

Impairments in hearing and vision impact on mortality in older people: the AGES-Reykjavik Study.

OBJECTIVE: to examine the relationships between impairments in hearing and vision and mortality from all-causes and cardiovascular disease (CVD) among older people. DESIGN: population-based cohort study. PARTICIPANTS: the study population included 4,926 Icelandic individuals, aged ≥67 years, 43.4% male, who completed vision and hearing examinations between 2002 and 2006 in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-RS) and were followed prospectively for mortality through 2009. METHODS: participants were classified as having 'moderate or greater' degree of impairment for vision only (VI), hearing only (HI), and both vision and hearing (dual sensory impairment, DSI). Cox proportional hazard regression, with age as the time scale, was used to calculate hazard ratios (HR) associated with impairment and mortality due to all-causes and specifically CVD after a median follow-up of 5.3 years. RESULTS: the prevalence of HI, VI and DSI were 25.4, 9.2 and 7.0%, respectively. After adjusting for age, significantly (P < 0.01) increased mortality from all causes, and CVD was observed for HI and DSI, especially among men. After further adjustment for established mortality risk factors, people with HI remained at higher risk for CVD mortality [HR: 1.70 (1.27-2.27)], whereas people with DSI remained at higher risk of all-cause mortality [HR: 1.43 (1.11-1.85)] and CVD mortality [HR: 1.78 (1.18-2.69)]. Mortality rates were significantly higher in men with HI and DSI and were elevated, although not significantly, among women with HI. CONCLUSIONS: older men with HI or DSI had a greater risk of dying from any cause and particularly cardiovascular causes within a median 5-year follow-up. Women with hearing impairment had a non-significantly elevated risk. Vision impairment alone was not associated with increased mortality.

Patterns of abstinence or continued drug use among methadone maintenance patients and their relation to treatment retention.

The efficacy and effectiveness of methadone maintenance treatment (MMT) in the medical management of opioid addiction has been well-established, but treatment outcomes are compromised by the continued use of licit and illicit drugs during MMT. The present study examined the relationship between in-treatment illicit drug use and retention and dropout of 604 MMT patients in Washington, D.C. Sixty-eight percent of patients did not test positive for an unprescribed drug during the study period. Of patients who tested positive for an illicit drug during the baseline period, 55% tested positive for cocaine, 44% for opiates, 23% for THC, 20% for benzodiazepines, 7% for PCP, and 4% for amphetamines. Those testing positive were three times more likely to leave treatment than those who did not test positive. Testing positive for one drug doubled the rate of attrition; testing positive for multiple drugs quadrupled the risk of attrition. Non-prescribed opioid or benzodiazepine use was a predictor of MMT dropout, but prescribed opioid or benzodiazepine use was not. Continued illicit drug use poses significant risk for subsequent premature termination of MMT. Assertive clinical management of continued illicit drug use could provide mechanisms to enhance MMT retention and long-term recovery outcomes.

Semiparametric partial linear modeling of risk factors for ear infections: the Early Childhood Longitudinal Study.

The Early Childhood Longitudinal Study-Kindergarten Class of 2010-2011 (ECLS-K:2011) ascertained timing of ear infections within age specified intervals and parent's/caregiver's report of medically diagnosed hearing loss. In this nationally representative, school-based sample of children followed from kindergarten entry through fifth grade, academic performance in reading, mathematics, and science was assessed longitudinally. Prior investigations of this ECLS-K:2011 cohort showed that age has a non-linear, monotonically increasing functional relationship with academic performance. Because of this knowledge, a semiparametric partial linear model is proposed, in which the effect of age is modeled by an unknown monotonically increasing function along with other regression parameters. The parameters are estimated by a semiparametric maximum likelihood estimator. A test of a constant effect of age is also proposed. Simulation studies are conducted to evaluate the performance of the proposed method, as compared with the commonly used linear model; the former outperforms the latter based on several criteria. We then analyzed ECLS-K:2011 data to compare results of the partial linear parametric model estimation with that of classical linear regression models.